Affinage

HAND1

Heart- and neural crest derivatives-expressed protein 1 · UniProt O96004

Length
215 aa
Mass
23.6 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 48 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HAND1 is a class B basic helix-loop-helix (bHLH) transcription factor that functions as a concentration-dependent fate determinant in multiple developmental lineages, including trophoblast giant cell differentiation, left ventricular cardiomyocyte identity, extraembryonic mesoderm specification, and placental vascular development (PMID:7671815, PMID:9500551, PMID:40164946, PMID:34502440). HAND1 activates target genes such as ANF/Nppa (via MEF2 tethering and CBP co-recruitment), Thymosin β4 (via non-canonical E-boxes), and pro-apoptotic CHOP/BAK, while repressing lipid metabolism programs downstream of HIF1α, steroidogenic genes (aromatase, P450scc via ALKBH1-mediated promoter methylation), and other bHLH targets through E-protein competition and DNA-binding-independent corepression (PMID:16043483, PMID:20975697, PMID:24086110, PMID:34391879, PMID:36594085). Its activity is regulated at multiple levels: nucleolar sequestration by I-mfa domain proteins is relieved by Plk4-mediated phosphorylation to permit nuclear function, JNK phosphorylation at Ser48 triggers proteasomal degradation (antagonized by vitamin C), and phosphorylation-dependent shifts between homodimer and heterodimer states control transcriptional output and tissue patterning, with the homodimer being sufficient for viability (PMID:17891141, PMID:39008099, PMID:23911935, PMID:25053435). Upstream, HAND1 expression is directly activated by BMP/Smad signaling and GATA4 through a left ventricle-specific enhancer, and loss-of-function HAND1 mutations are associated with human hypoplastic hearts, septation defects, and familial dilated cardiomyopathy (PMID:34576009, PMID:31366290, PMID:18276607, PMID:26581070).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1995 High

    Identification of HAND1 as a bHLH transcription factor that heterodimerizes with E12 and drives trophoblast differentiation established its founding functional identity as a lineage-determining transcription factor.

    Evidence Yeast two-hybrid identification of E12 interaction; overexpression in mouse blastomeres and Rcho-1 trophoblast stem cells inducing differentiation and placental lactogen-I promoter activation

    PMID:7649392 PMID:7671815

    Open questions at the time
    • No direct DNA-binding site or target gene identified
    • Mechanism by which HAND1 overrides stem cell identity unknown
  2. 1998 High

    Knockout studies revealed that HAND1 has separable essential roles in extraembryonic mesoderm/yolk sac development and in cardiac morphogenesis, with ventricular identity specification independent of left-right body axis.

    Evidence Hand1-null embryos die E8.5-9.5 with extraembryonic mesoderm and cardiac looping defects; tetraploid chimera rescue isolates cardiac-autonomous role; inv/inv situs inversus mice show HAND1 marks systemic ventricle regardless of anatomical side

    PMID:9500550 PMID:9500551 PMID:9576835

    Open questions at the time
    • Downstream target genes of HAND1 in each lineage unidentified
    • Mechanism of ventricular identity specification unknown
  3. 2000 High

    Biochemical dissection showed HAND1 functions through multiple mechanisms — homodimerization, heterodimerization with HAND2/E-proteins/HRT factors, E-protein sequestration, and DNA-binding-independent corepression — explaining how a single factor can both activate and repress transcription.

    Evidence Yeast and mammalian two-hybrid, pulldown, EMSA competition assays for dimerization; tethered MyoD-E47 dimer experiments demonstrating corepression independent of DNA binding; HAND1-MASH2 genetic double mutant showing additional mechanisms beyond E-factor competition

    PMID:10611232 PMID:10837146 PMID:10924525

    Open questions at the time
    • In vivo dimerization partners in specific tissues not resolved
    • No chromatin-level mechanism established
  4. 2004 High

    Conditional and chimeric analyses established that HAND1 controls the proliferation-differentiation balance in cardioblasts, drives trophoblast giant cell fate even against mitogenic FGF4 signaling, and patterns ventricular wall expansion, while revealing partial redundancy with HAND2.

    Evidence Cardiac-specific Hand1 CKO and Hand1/Hand2 double mutants; Hand1 gain-of-function knock-in under MLC2V; chimeric analysis of Hand1-null ES cells in hearts; TS cell overexpression overriding FGF4

    PMID:11076684 PMID:15143159 PMID:15196947 PMID:15576406

    Open questions at the time
    • Direct transcriptional targets mediating ventricular patterning unknown
    • Mechanism of FGF4 override uncharacterized
  5. 2005 High

    ANF/Nppa was identified as the first direct HAND1 target gene, revealing that HAND1 activates cardiac promoters not through canonical E-box binding but via tethering to MEF2 proteins with CBP co-recruitment, fundamentally reframing HAND1's mode of transcriptional activation.

    Evidence Luciferase reporters, co-immunoprecipitation of HAND1-MEF2 complex, domain deletion studies showing E-box independence

    PMID:16043483

    Open questions at the time
    • Genome-wide binding profile not available
    • Whether MEF2 tethering applies to other HAND1 targets unclear
  6. 2007 High

    Discovery that HAND1 is held inactive by nucleolar sequestration and released by Plk4 phosphorylation revealed a cell-cycle-coupled mechanism gating trophoblast stem cell commitment to giant cell fate.

    Evidence Co-IP of HAND1 with I-mfa domain protein, live imaging of nucleolar-to-nuclear translocation, Plk4 kinase assay, Rcho-1 differentiation

    PMID:17891141

    Open questions at the time
    • Plk4 phosphorylation site on HAND1 not mapped
    • Whether nucleolar sequestration operates in cardiac lineage unknown
  7. 2010 High

    ChIP demonstrated Thymosin β4 as a direct HAND1 target via canonical and non-canonical E-boxes, and synthetic Tβ4 partially rescued yolk sac vasculogenesis in Hand1-null embryos, establishing a HAND1→Tβ4 axis in vascular development.

    Evidence ChIP of HAND1 on Tβ4 promoter, reporter assays distinguishing canonical vs. non-canonical E-box function, Tβ4 protein rescue of Hand1-null yolk sac capillary plexus

    PMID:20975697

    Open questions at the time
    • Other direct targets driving vasculogenesis not identified
    • Mechanism of Tβ4 in vessel remodeling downstream of HAND1 not resolved
  8. 2013 High

    Two key advances established that HAND1 functions primarily as a homodimer in vivo (tethered homodimer knock-in mice are viable) and that HIF1α directly drives Hand1 to suppress lipid metabolism genes and maintain glycolytic state in embryonic cardiomyocytes, linking HAND1 to metabolic reprogramming.

    Evidence Tethered homodimer knock-in mouse viability/fertility; HIF1α transcription assays, transgenic Hand1 overexpression preventing neonatal lipid gene activation, Hand1 CKO causing premature lipid gene expression, metabolic flux analysis, ischemia protection model

    PMID:23911935 PMID:24086110

    Open questions at the time
    • Specific lipid metabolism genes directly repressed by HAND1 not identified by ChIP
    • Homodimer vs heterodimer contribution to metabolic regulation unclear
  9. 2014 High

    Phosphoregulation of HAND1 dimerization was shown to be the critical parameter in craniofacial and limb development: phospho-mutant knock-ins cause severe midface clefting and limb truncation through non-cell-autonomous cell death and disrupted signaling (Fgf8, Shh, Gli3), while simple Hand1 deletion is tolerated in neural crest cells.

    Evidence Conditional phospho-site mutant knock-in vs. CKO in NCCs (Wnt1-Cre) and limb (Prrx1-Cre); genetic rescue by reducing Hand2/Shh dosage

    PMID:25053435 PMID:28576769

    Open questions at the time
    • Kinase(s) responsible for this phosphoregulation in NCCs and limb not identified
    • How altered dimer pool causes non-cell-autonomous death mechanistically unknown
  10. 2019 High

    A left ventricle-specific Hand1 enhancer was mapped containing GATA4-bound cis-elements; its CRISPR deletion or disruption by a human SNP causes conduction system defects, connecting a human genetic variant to HAND1-dependent cardiac electrophysiology.

    Evidence CRISPR/Cas9 enhancer deletion, EMSA confirming GATA4 binding, electrophysiology showing right bundle branch block, SNP (rs10054375) modeling in mice

    PMID:31366290

    Open questions at the time
    • Whether other enhancers control HAND1 expression in non-cardiac tissues unknown
    • Full regulatory landscape of HAND1 locus not characterized
  11. 2021 High

    Multiple mechanisms of HAND1-mediated steroidogenic repression in trophoblasts were uncovered — direct aromatase promoter binding, ALKBH1-dependent P450scc promoter methylation, and HuR-mediated mRNA destabilization — expanding HAND1's role beyond classical transcriptional activation/repression to include epigenetic and post-transcriptional control.

    Evidence ChIP on aromatase and P450scc promoters, co-IP of HAND1 with ALKBH1 and HuR, methylation assays, mRNA stability assays, JEG-3 xenograft

    PMID:34391879

    Open questions at the time
    • Whether ALKBH1-mediated mechanism operates at other HAND1 targets unknown
    • In vivo relevance of HuR interaction not validated in primary trophoblasts
  12. 2021 High

    BMP/Smad signaling was shown to directly bind and activate the Hand1 gene, and Hand1 was shown essential for placental labyrinth vascular formation throughout pregnancy, closing a major gap in upstream regulation and extending HAND1's placental role beyond early trophoblast differentiation.

    Evidence ChIP demonstrating Smad binding to Hand1; Bmp2/Bmp4 loss/gain-of-function embryos; two Cre-driven placental Hand1 CKOs (Nkx2-5-Cre, Cdh5-Cre) with vessel density quantification

    PMID:34502440 PMID:34576009

    Open questions at the time
    • Specific Smad isoforms and binding sites fully contributing to Hand1 regulation not resolved
    • Whether BMP dose controls Hand1 concentration-dependent fate switching is untested
  13. 2024 High

    JNK was identified as the kinase phosphorylating HAND1 at Ser48 to trigger proteasomal degradation, and vitamin C was shown to stabilize HAND1 by inactivating JNK, revealing a nutrient-responsive post-translational mechanism controlling trophoblast differentiation.

    Evidence Ser48 mutagenesis, JNK inhibition/activation, proteasome inhibitor experiments, trophoblast differentiation assays in mice

    PMID:39008099

    Open questions at the time
    • Relationship between Ser48 (JNK) and Plk4 phosphorylation sites unclear
    • Whether vitamin C-JNK-HAND1 axis is relevant in cardiac tissue not tested
  14. 2025 High

    HAND1 concentration was demonstrated to be the binary switch between cardiac/epicardial progenitor (low) and extraembryonic mesoderm (high) fates in human iPSCs, and HAND1 was found to bind ape-specific LTR2B retroviral elements contributing to human-specific ExMC gene regulation.

    Evidence hPSC differentiation with controlled HAND1 levels and CRISPR knockout; ChIP-seq/ATAC-seq identifying HAND1 binding at LTR2B elements

    PMID:40164946 PMID:40220298

    Open questions at the time
    • Mechanism by which HAND1 concentration is read out by the cell fate machinery unknown
    • Functional contribution of individual LTR2B-bound loci not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • A comprehensive genome-wide map of direct HAND1 binding sites across its key developmental contexts (trophoblast, cardiomyocyte, extraembryonic mesoderm), and the structural basis for how phosphorylation switches dimer preference and target selection, remain unresolved.
  • No crystal or cryo-EM structure of HAND1 homodimer or heterodimer
  • Genome-wide ChIP-seq in primary cardiac and trophoblast tissues not reported beyond LTR2B analysis
  • Quantitative relationship between HAND1 protein concentration thresholds and fate commitment not mechanistically defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 8 GO:0003677 DNA binding 6
Localization
GO:0005634 nucleus 2 GO:0005730 nucleolus 1
Pathway
R-HSA-74160 Gene expression (Transcription) 8 R-HSA-1266738 Developmental Biology 7 R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-5357801 Programmed Cell Death 1
Partners
ALKBH1E12FHL2GATA4HAND2MEF2PLK4SOX15

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 HAND1 (Hxt/eHAND) encodes a bHLH transcription factor that, when overexpressed in mouse blastomeres, directs their development into trophoblast cells and induces differentiation of rat trophoblast (Rcho-1) stem cells, as shown by changes in cell adhesion and activation of the placental lactogen-I gene promoter; the negative HLH regulator Id-1 inhibits this differentiation. Overexpression in blastomeres, Rcho-1 trophoblast stem cell differentiation assay, reporter gene activation Development (Cambridge, England) High 7671815
1995 eHAND (HAND1) was identified via yeast two-hybrid screening as a novel class B bHLH protein that heterodimerizes with the ubiquitously expressed class A bHLH protein E12, placing it in the bHLH interaction network. Yeast two-hybrid screen with E12 as bait Developmental biology Medium 7649392
1997 Left-sided eHAND (HAND1) expression in the heart requires the homeobox transcription factor Nkx2-5; in Nkx2-5-null mice that fail to loop, eHAND expression is abolished, establishing Nkx2-5 as an upstream regulator of HAND1 in cardiac L/R asymmetry. Genetic epistasis — analysis of eHand expression in Nkx2-5-null, Sc1-/-, and inv/inv mouse mutant embryos Genes & development High 9192865
1998 Hand1-null mice die by E8.5–9.5 with yolk sac abnormalities due to extraembryonic mesoderm deficiency and cardiac looping arrest, demonstrating Hand1 is essential for extraembryonic mesodermal and early heart development. Germline gene targeting (knockout); homozygous null embryo analysis Nature genetics High 9500550 9500551
1998 Hand1-null embryos rescued by tetraploid complementation (restoring wild-type trophoblast) die at E10.5 from cardiac failure with abnormal looping and ventricular myocardial differentiation, demonstrating a cell-autonomous role for Hand1 in cardiomyocyte differentiation separate from its trophoblast role. Tetraploid chimera rescue of Hand1-null embryos; histological and cardiac analysis Nature genetics High 9500551
1998 eHAND (HAND1) and dHAND (HAND2) mark the systemic (left) and pulmonary (right) ventricles respectively, independent of left-right sidedness — in situs inversus (inv/inv) mice the anatomical positions are reversed but HAND gene chamber assignments are maintained, indicating HAND factors specify ventricular identity rather than control looping direction. Expression analysis in inv/inv situs inversus mice; dHAND/inv double mutant analysis Developmental biology High 9576835
1998 Xenopus eHAND expression is strongly induced in animal cap explants by BMP-2 and BMP-4, and this induction is blocked by a dominant-negative BMP receptor, placing eHAND downstream of BMP signaling in cardiovascular development. Animal cap explants, ectopic BMP-2/BMP-4 expression, dominant-negative BMP receptor co-expression Mechanisms of development Medium 9507100
2000 HAND1 (eHAND) and HAND2 (dHAND) form homodimers (HAND1/HAND1, HAND2/HAND2) and heterodimers (HAND1/HAND2) in vivo, as demonstrated by yeast two-hybrid, mammalian two-hybrid, and biochemical pulldown assays. They also heterodimerize with HRT1-3 (Hairy-related transcription factors). Competition gel shift analysis shows HAND1 and HAND2 can negatively regulate MyoD/E12 heterodimer DNA binding. Yeast two-hybrid, mammalian two-hybrid, biochemical pulldown, electrophoretic mobility shift assay (EMSA) competition The Journal of biological chemistry High 10924525
2000 HAND1 antagonizes MASH2 function in trophoblast development by competing for E-factor binding; HAND1 and MASH2 both heterodimerize with E factors (ITF2, ALF1) in the ectoplacental cone and spongiotrophoblast. However, the Hand1 mutant phenotype is not altered by further Mash2 mutation, indicating additional mechanisms. HAND1 can also suppress E-factor transcriptional activity directly. In vitro dimerization assays, genetic double-mutant analysis (Hand1/Mash2), reporter gene assays, expression analysis Molecular and cellular biology High 10611232
2000 eHAND (HAND1) acts as a transcriptional inhibitor of selected bHLH proteins (e.g., MyoD) by: (1) preventing E-box DNA binding by competing for E-protein partners, (2) acting as a corepressor independently of DNA binding (shown using tethered MyoD-E47 dimer), and (3) inhibiting MyoD-dependent skeletal muscle differentiation, including suppression of myosin heavy chain expression. Transient transfection reporter assays, tethered dimer constructs, myogenic differentiation assays Experimental cell research High 10837146
2000 Hand1-null cells are excluded from specific regions of the left caudal linear heart tube at E8.0 and from the anterior outer curvature of the left ventricular myocardium at E9.5 in chimeric mouse embryos, demonstrating a cell-autonomous function of Hand1 in cardiac morphogenesis. Hand1-null cells can still differentiate into beating cardiomyocytes in vitro, indicating Hand1 is not essential for cardiomyocyte differentiation per se. Chimeric mouse analysis (Hand1-null ES cells + ROSA26 embryos), in vitro ES cell differentiation Developmental biology High 11076684
2002 Human HAND1 heterodimerizes with E12/E47 (E factors) and stimulates transcription from degenerate E-box reporters, but inhibits E12/E47-dependent transcription from perfect palindromic E-box reporters by blocking heterodimer-DNA interaction. HAND1 also directly represses GAL-E12-driven reporter expression. Mutational analysis identifies two N-terminal regions as the main repressor domains. Luciferase reporter assays, GAL4 fusion constructs, in vitro dimerization, mutational analysis of repression domains The Biochemical journal High 11802795
2002 Thymosin β4 (Tmsb4x) is identified as a putative downstream target of Hand1, being downregulated in Hand1-null embryoid bodies; cystatin C and alphaCA are upregulated. These genes show co-expression with Hand1 in wild-type hearts and aberrant expression in Hand1-null embryos. Representational difference analysis (differential screen), whole-mount in situ hybridization on wild-type and Hand1-null embryos Mechanisms of development Medium 14516662
2004 Cardiac-specific deletion of Hand1 (using cardiac Cre) causes left ventricular and endocardial cushion defects with dysregulated ventricular gene expression. Hand1/Hand2 double mutants reveal gene dose-sensitive roles, demonstrating partial functional redundancy between Hand1 and Hand2 in cardiac morphogenesis and cardiomyocyte differentiation. Conditional knockout (cardiac-specific Cre), Hand1/Hand2 double mutant analysis Development (Cambridge, England) High 15576406
2004 HAND1 promotes trophoblast giant cell (TGC) differentiation even in the presence of FGF4/CM (which normally maintains stem cell identity), demonstrating that HAND1 overrides FGF4 mitogenic signaling to drive terminal TGC differentiation. HAND1 promotes cell cycle exit and restriction to the TGC fate. Ectopic expression in trophoblast stem (TS) cells in the presence of FGF4/CM, proliferation and differentiation assays Developmental biology High 15196947
2004 HAND1 is required for extra-embryonic vasculature development: Hand1-null yolk sacs undergo vasculogenesis but arrest in vascular refinement. Angiogenic genes including VEGF, Ang1, ephrin B2, and Notch pathway components are upregulated. Smooth muscle cells fail to be recruited to peri-endothelial tissue and instead differentiate in ectopic clusters. Hand2 upregulation in Hand1-null yolk sacs is insufficient to compensate. Hand1 knockout mouse analysis, gene expression profiling in yolk sac, histological and molecular analysis Development (Cambridge, England) High 15073150
2004 HAND1 expression in knock-in mice (under MLC2V promoter) causes expansion of the outer curvature of both ventricles and abolishes interventricular groove and septum formation, without affecting the inner curvature, AV canal, or outflow tract. HAND1 alters expression of Chisel, ANF, and Hand2/dHAND but not Tbx5, indicating HAND1 controls dorso-ventral ventricular patterning and is involved in ventricular wall expansion rather than being a master left-ventricular lineage specifier. Hand1/eHAND knock-in mice under MLC2V promoter, gene expression analysis Molecular and cellular biology High 15143159
2004 CLP-1 (cardiac lineage protein-1) ablation in mice leads to significant downregulation of HAND1 in fetal hearts, suggesting CLP-1 acts upstream of HAND1 in a cardiac developmental gene regulatory program. CLP-1 knockout mouse, gene expression analysis of HAND1 in fetal hearts Mechanisms of development Medium 15172687
2004 FHL2 (a LIM domain protein/transcriptional coactivator) interacts with HAND1 via the bHLH domain. FHL2 represses HAND1/E12 heterodimer-induced transcription but has no effect on HAND1/HAND1 homodimer activity, defining a differential post-dimerization regulatory mechanism for HAND1. Co-immunoprecipitation, GST pulldown, reporter gene assays with FHL2, dimerization assays Molecular and cellular biology High 15509787
2005 HAND1 directly activates the cardiac atrial natriuretic factor (ANF/Nppa) promoter, the first identified HAND1 transcriptional target. HAND1 is recruited to the ANF promoter via physical interaction with MEF2 proteins (not through E-box elements or heterodimerization with class I bHLH factors). MEF2/HAND1 interaction results in synergistic activation of MEF2-dependent promoters, likely via co-recruitment of CREB-binding protein (CBP). Luciferase reporter assays, co-immunoprecipitation (HAND1-MEF2 interaction), chromatin recruitment analysis, domain deletion studies The Journal of biological chemistry High 16043483
2006 Sox15 interacts physically with HAND1 in co-transfected 293T cells and in vitro, and enhances HAND1-driven transcription in a manner requiring both the Hand1-binding region and Sox15's transactivation domain. Hand1 overexpression represses Sox15-driven reporter expression, while Sox15 enhances Hand1-driven transcription to promote trophoblast giant cell differentiation. Co-immunoprecipitation in 293T cells, in vitro binding, luciferase reporter assay, Rcho-1 trophoblast differentiation assay Differentiation; research in biological diversity Medium 16759287
2006 Upregulation of HAND1 restricted to Hand1-expressing cardioblasts causes extended heart tube and extraneous looping through elevated proliferation of distal outflow tract cardioblasts (G1 progression, increased cell division, prevention of cell-cycle exit). In Hand1-null ES cell-derived cardiomyocytes, cardiomyocyte differentiation is elevated, establishing HAND1 as a regulator of the balance between cardioblast proliferation and differentiation. Hand1 gain-of-function transgenic mice, ES cell-derived cardiomyocyte differentiation assays in Hand1-null background, cell-cycle analysis Development (Cambridge, England) High 17050624
2007 HAND1 is sequestered in the nucleolus (inactive state) by interaction with an I-mfa domain-containing protein, anchoring it away from target genes during trophoblast stem cell proliferation. Site-specific phosphorylation of HAND1 by the polo-like kinase Plk4 (Sak) — which localizes to the nucleolus during G2 — releases HAND1 from the nucleolus into the nucleus, enabling its activation and commitment of trophoblast stem cells to a giant-cell fate. Co-immunoprecipitation (HAND1-I-mfa domain protein), subcellular localization (live imaging/fractionation), phosphorylation assay (Plk4/Sak kinase), functional differentiation assay in Rcho-1 cells Nature cell biology High 17891141
2008 A frameshift mutation (A126fs) in the bHLH domain of HAND1 found in 24/31 human hypoplastic hearts renders the protein unable to modulate transcription of reporter constructs containing specific DNA-binding sites, demonstrating loss-of-function via disruption of DNA-binding/combinatorial interaction. Sequencing of human heart tissue, luciferase reporter assay comparing wild-type vs. mutant HAND1 Human molecular genetics Medium 18276607
2009 Overexpression of HAND1 in adult mouse hearts causes loss of connexin43 protein from cardiac intercalated discs, increased intercalated disc beta-catenin expression at protein and RNA levels, and a greatly reduced threshold for induced ventricular tachycardia (arrhythmia), without significant fibrosis or heart failure. Inducible transgenic overexpression in adult mice, electrophysiology, protein/RNA expression analysis Journal of molecular and cellular cardiology High 19376125
2009 HAND1 mutations identified in human hearts with septation defects reduce or abolish HAND1 transcriptional activity (e.g., L138P), as demonstrated by reporter assays in both yeast and mammalian cells. Sequencing of cardiac tissue, dual-reporter functional assays in yeast and mammalian cells Human molecular genetics Medium 19586923
2010 HAND1 is expressed within the septum transversum, and the Hand1 lineage marks the proepicardial organ and epicardium. Conditional deletion of Hand2 from Hand1-expressing cells causes defective epicardialization and failure to form coronary arteries, with altered extracellular matrix deposition and Pdgfr expression, establishing a hierarchal Hand1→epicardial precursor→Hand2-dependent coronary artery pathway. Hand1-Cre lineage tracing, conditional Hand2 deletion in Hand1-expressing cells, histological and molecular analysis Circulation research High 21350214
2010 Thymosin β4 (Tβ4) is a direct transcriptional target of HAND1. HAND1 binds an upstream regulatory region proximal to the Tβ4 promoter at consensus Thing1 and E-Box sites. HAND1 can either activate (via non-canonical E-boxes) or repress (via canonical E-boxes) Tβ4. Hand1-mediated activation of Tβ4 is essential for yolk sac vasculogenesis; synthetic Tβ4 partially rescues capillary plexus formation in Hand1-null embryos. ChIP (HAND1 binding to Tβ4 promoter), reporter gene assays, rescue experiment with synthetic Tβ4 protein in Hand1-null embryos Nature communications High 20975697
2011 Stress stimuli activate SAPK (MAPK8/9), which is required for induction of HAND1 protein in trophoblast stem cells; MAPK8/9 inhibitors block HAND1 upregulation by stress. HAND1 induction depends upstream on EOMES and downstream drives CSH1 expression, placing HAND1 within a stress-responsive transcriptional cascade in trophoblast differentiation. Immunocytochemistry, immunoblot, MAPK8/9 pharmacological inhibitors (LJNKl1, SP600125) in trophoblast stem cells Molecular reproduction and development Medium 21710638
2012 A 1007 bp cis-regulatory element 5' of Hand1 drives reporter expression in the sympathetic chain of transgenic mice. ChIP and EMSA confirm that Hand2 and Phox2b bind evolutionarily conserved consensus sites (E-boxes and Phox2 sites) within this element. Hand2 is required in a gene dose-dependent manner for reporter activation in sympathetic neurons, while Hand1 is dispensable for TH and DBH expression even when Hand2 dosage is reduced. Transgenic reporter mouse, ChIP, EMSA, Hand2 conditional null and hypomorphic backgrounds, TH/DBH expression analysis The Journal of neuroscience High 22323723
2013 HIF1α directly controls Hand1 transcription in cardiomyocytes. HAND1 expression inhibits lipid metabolism gene expression programs, reducing mitochondrial energy generation and increasing lactate production from glucose. Transgenic mice with prolonged cardiac HAND1 fail to activate neonatal lipid-metabolizing gene programs and die at birth. Embryonic cardiomyocyte Hand1 deletion causes premature expression of lipid-metabolizing genes. Upregulation of Hand1 is protective in a mouse model of myocardial ischemia. HIF1α-driven transcription assays, transgenic overexpression, embryonic conditional deletion, metabolic flux analysis, mouse ischemia model PLoS biology High 24086110
2013 Hand1 functions predominantly as a homodimer in vivo: mice in which the only form of Hand1 is an engineered tethered homodimer (Hand1-TH) can be viable and fertile, demonstrating that Hand1 homodimer activity is sufficient. Hand1 heterodimers appear dispensable or serve a regulatory/modulatory role. Tethered homodimer knock-in mouse model, viability and fertility analysis, comparison to Hand1 null Developmental biology High 23911935
2014 Altering Hand1 phosphoregulation (and consequently dimerization affinities) in neural crest cells causes severe mid-facial clefting and neonatal death via a non-cell-autonomous increase in pharyngeal arch cell death with altered Fgf8 and Shh pathway expression. Hand1 deletion in NCCs alone reveals a non-essential role, confirming that dimer phosphoregulation rather than Hand1 presence per se is critical. Conditional phosphorylation-site mutant knock-in in NCCs, conditional knockout in NCCs, histology, Fgf8/Shh expression analysis Development (Cambridge, England) High 25053435
2014 Elf5 knockdown in trophoblast stem cells leads to rapid loss of Sox2/3 expression and transient upregulation of Hand1, demonstrating that Elf5 normally suppresses Hand1 expression to counteract precocious TGC differentiation; Elf5 acts as a gatekeeper for the TS-to-differentiated trophoblast transition. Elf5 siRNA knockdown in TS cells, expression analysis of Hand1 and Sox2/3, ES-to-TS differentiation assay with Cdx2 overexpression Developmental biology Medium 24859262
2014 miR-363 negatively regulates HAND1 post-transcriptionally: miR-363 overexpression reduces HAND1 mRNA and protein in hESC-derived cardiomyocytes, and a dual luciferase assay demonstrates direct functional interaction of miR-363 with the full-length HAND1 3'UTR. Anti-miR-363 enriches for HAND1-expressing cardiomyocyte subtype populations. miRNA overexpression/inhibition, dual luciferase reporter assay with HAND1 3'UTR, flow cytometry/population analysis Stem cell research & therapy Medium 24906886
2016 HAND1 overexpression in osteochondral progenitors in mice results in prenatal hypoplastic/aplastic ossification mimicking Ihh loss-of-function. HAND1 downregulates Ihh gene expression and inhibits Runx2 transactivation of the Ihh proximal promoter in vitro, placing Hand1 in the Runx2-Ihh axis regulating endochondral ossification. Transgenic Hand1 overexpression in osteochondral progenitors, Ihh expression analysis, in vitro Runx2-Ihh promoter reporter assay PloS one Medium 26918743
2016 HAND1 R105X (nonsense) mutation found in familial DCM abolishes HAND1 transcriptional activity and eliminates synergistic transcriptional activation between HAND1 and GATA4, as shown by dual-luciferase reporter assays. Gene sequencing, dual-luciferase reporter assay, HAND1/GATA4 co-activation assay Clinical chemistry and laboratory medicine Medium 26581070
2017 Altering Hand1 phosphoregulation in developing vertebrate limbs (phospho-mutant knock-in via Prrx1-Cre) results in severe truncation of proximal-anterior limb elements via a non-cell-autonomous mechanism causing widespread cell death, with reduction of Irx3, Irx5, Gli3, and Alx4 expression. Reducing Hand2 and Shh gene dosage improves anterior limb integrity, validating the importance of HAND family bHLH dimer pool balance. Conditional phospho-mutant knock-in (Prrx1-Cre), conditional knockout, Hand2/Shh genetic interaction (dosage reduction), cell death analysis, gene expression Development (Cambridge, England) High 28576769
2019 A left ventricle-specific HAND1 enhancer contains two evolutionarily conserved GATA transcription factor cis-binding elements bound by GATA4 (shown by EMSA and in vitro DNA binding assays). CRISPR/Cas9 deletion of this enhancer reduces Hand1 expression specifically in the LV and results in morphologically abnormal ventricular conduction system and right bundle branch block. A human SNP (rs10054375) within a critical GATA element disrupts GATA4 DNA binding and, when modeled in mice, causes diminished Hand1 expression and VCS dysfunction. CRISPR/Cas9 enhancer deletion, EMSA (GATA4 binding), transgenic reporter mice, electrophysiology (VCS analysis), SNP modeling in mice Circulation research High 31366290
2020 Myocardial deletion of Hand1 (using Nkx2.5-Cre or αMhc-Cre) results in survivable cardiac morphogenetic defects including conduction system defects, interventricular septal defects, and abnormal left ventricular papillary muscles, progressing to diastolic heart failure in adults. Transcriptome analysis identifies disrupted translation and cardiac hypertrophy-related pathways. Conditional knockout (Nkx2.5-Cre, αMhc-Cre), histology, echocardiography, electrophysiology, transcriptome/IPA pathway analysis Cardiovascular research High 31286141
2021 HAND1 inhibits human trophoblast progesterone and estradiol biosynthesis by: (1) directly binding the aromatase gene promoter to repress transcription; (2) upregulating methylation of the P450scc gene promoter via binding to the demethylase ALKBH1; and (3) decreasing 3β-HSD1 mRNA stability by binding to and destabilizing HuR. These mechanisms collectively suppress steroidogenesis in human trophoblasts. ChIP (HAND1 binding to aromatase and P450scc promoters), co-immunoprecipitation (HAND1-ALKBH1, HAND1-HuR), methylation assays, mRNA stability assays, JEG-3 xenograft hormone measurements Journal of genetics and genomics High 34391879
2021 Conditional mutation of Hand1 in placenta (Nkx2-5-Cre for early, Cdh5-Cre for late pregnancy) causes embryonic lethality due to failure of placental labyrinth formation, with significantly reduced labyrinthine vessel density, demonstrating that Hand1 is required for placental vascular establishment and remodeling beyond early pregnancy. Conditional knockout (Nkx2-5-Cre and Cdh5-Cre), histology, vessel density quantification, angiogenic factor mRNA analysis International journal of molecular sciences High 34502440
2021 BMP signaling directly regulates Hand1 expression in a dose-dependent manner during cardiac development: Hand1 is decreased in Bmp2/Bmp4 loss-of-function embryos and increased in Bmp4 gain-of-function embryos. ChIP and transfection assays demonstrate that Smads directly activate and bind the Hand1 gene; BMP2/BMP4 treatment of P19 cells induces Hand1 expression and cardiac differentiation. Bmp2/Bmp4 loss- and gain-of-function mouse embryos, ChIP (Smad binding to Hand1), transfection reporter assays, P19 cell cardiac differentiation International journal of molecular sciences High 34576009
2023 HAND1 inhibits gastric cancer cell growth by inducing ER stress/mitochondria-mediated apoptosis via direct transcriptional binding to CHOP and BAK promoters, positively regulating BAK transcription. HAND1 also physically interacts with CHOP. Knockdown of CHOP or BAK attenuates HAND1-induced apoptosis; CHOP overexpression increases BAK expression. Ectopic HAND1 expression in GC cells, ChIP (HAND1 binding CHOP and BAK promoters), co-immunoprecipitation (HAND1-CHOP), siRNA knockdown of CHOP/BAK, in vitro and in vivo (xenograft) growth assays International journal of biological sciences High 36594085
2024 Vitamin C stabilizes HAND1 by inactivating JNK signaling: JNK directly phosphorylates HAND1 at Ser48, triggering its proteasomal degradation. Vitamin C treatment inactivates JNK, thereby preventing Hand1 degradation and promoting trophoblast giant cell differentiation. A Ser48 loss-of-function mutant is refractory to both intrinsic and VC-induced stabilization. Phosphorylation site mutagenesis (Ser48), JNK inhibition/activation assays, proteasome inhibitor experiments, lentiviral knockdown, trophoblast differentiation assays in mice Cellular and molecular life sciences High 39008099
2025 HAND1 level determines cell fate in mesodermal progenitors from human pluripotent stem cells in a concentration-dependent manner: low HAND1 directs differentiation toward multipotent juxta-cardiac field progenitors (capable of cardiomyocytes and epicardial cells), while high HAND1 promotes extraembryonic mesoderm development. HAND1-null cells remain in the trophoblast lineage, confirming HAND1 is essential for ExMC specification. hPSC differentiation model, HAND1 conditional knockout (CRISPR), controlled HAND1 expression levels, lineage reporter assays, transcriptomics The EMBO journal High 40164946
2025 Foxp1 directly regulates USP20 (a deubiquitinase that stabilizes HIF1α), and HIF1α in turn regulates HAND1 to control cardiomyocyte metabolic state (glycolysis vs. fatty acid oxidation); AAV9-mediated induction of Hand1 in cardiomyocytes promotes cardiac regeneration and functional recovery after myocardial infarction. Cardiomyocyte-specific Foxp1 loss- and gain-of-function, AAV9-Hand1 delivery in mice, myocardial infarction model, USP20/HIF1α pathway analysis Advanced science Medium 39899693
2025 HAND1 is essential for human extra-embryonic mesenchyme (ExMC) specification from iPSCs; HAND1-null cells remain in the trophoblast lineage. HAND1 binds ape-specific endogenous retrovirus-derived LTR2B elements that contribute to unique gene regulatory features of ExMC. HAND1 null iPSC model (CRISPR), ChIP-seq/ATAC-seq (HAND1 binding to LTR2B elements), lineage analysis Cell reports High 40220298

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 The Hand1 bHLH transcription factor is essential for placentation and cardiac morphogenesis. Nature genetics 434 9500551
1998 Heart and extra-embryonic mesodermal defects in mouse embryos lacking the bHLH transcription factor Hand1. Nature genetics 315 9500550
1995 Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Molecular and cellular biology 314 7862149
2004 The Hand1 and Hand2 transcription factors regulate expansion of the embryonic cardiac ventricles in a gene dosage-dependent manner. Development (Cambridge, England) 273 15576406
1995 Hxt encodes a basic helix-loop-helix transcription factor that regulates trophoblast cell development. Development (Cambridge, England) 273 7671815
1997 Homeodomain factor Nkx2-5 controls left/right asymmetric expression of bHLH gene eHand during murine heart development. Genes & development 247 9192865
1995 Identification of novel HXT genes in Saccharomyces cerevisiae reveals the impact of individual hexose transporters on glycolytic flux. Molecular microbiology 217 7651133
1995 Expression of the novel basic helix-loop-helix gene eHAND in neural crest derivatives and extraembryonic membranes during mouse development. Developmental biology 210 7649392
2000 The HAND1 basic helix-loop-helix transcription factor regulates trophoblast differentiation via multiple mechanisms. Molecular and cellular biology 195 10611232
1999 Glucose uptake kinetics and transcription of HXT genes in chemostat cultures of Saccharomyces cerevisiae. The Journal of biological chemistry 167 10336421
1998 The bHLH factors, dHAND and eHAND, specify pulmonary and systemic cardiac ventricles independent of left-right sidedness. Developmental biology 155 9576835
2003 Grr1-dependent inactivation of Mth1 mediates glucose-induced dissociation of Rgt1 from HXT gene promoters. Molecular biology of the cell 128 12925759
2004 The Hand1, Stra13 and Gcm1 transcription factors override FGF signaling to promote terminal differentiation of trophoblast stem cells. Developmental biology 123 15196947
2000 The basic helix-loop-helix transcription factors dHAND and eHAND exhibit dimerization characteristics that suggest complex regulation of function. The Journal of biological chemistry 86 10924525
2010 Analysis of the Hand1 cell lineage reveals novel contributions to cardiovascular, neural crest, extra-embryonic, and lateral mesoderm derivatives. Developmental dynamics : an official publication of the American Association of Anatomists 77 20882677
2008 A loss-of-function mutation in the binding domain of HAND1 predicts hypoplasia of the human hearts. Human molecular genetics 77 18276607
2004 Extra-embryonic vasculature development is regulated by the transcription factor HAND1. Development (Cambridge, England) 74 15073150
2011 Hand2 loss-of-function in Hand1-expressing cells reveals distinct roles in epicardial and coronary vessel development. Circulation research 65 21350214
2006 Hand1 regulates cardiomyocyte proliferation versus differentiation in the developing heart. Development (Cambridge, England) 64 17050624
2007 Nucleolar release of Hand1 acts as a molecular switch to determine cell fate. Nature cell biology 63 17891141
2009 A functional genetic study identifies HAND1 mutations in septation defects of the human heart. Human molecular genetics 58 19586923
2014 Directed differentiation of patient-specific induced pluripotent stem cells identifies the transcriptional repression and epigenetic modification of NKX2-5, HAND1, and NOTCH1 in hypoplastic left heart syndrome. PloS one 57 25050861
2004 Ablation of the CLP-1 gene leads to down-regulation of the HAND1 gene and abnormality of the left ventricle of the heart and fetal death. Mechanisms of development 55 15172687
2013 Hypoxic regulation of hand1 controls the fetal-neonatal switch in cardiac metabolism. PLoS biology 53 24086110
2002 Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression pattern, interaction partners and identification of its transcriptional repressor domains. The Biochemical journal 51 11802795
2013 DNA methylation status of NKX2-5, GATA4 and HAND1 in patients with tetralogy of fallot. BMC medical genomics 48 24182332
2004 Differential regulation of Hand1 homodimer and Hand1-E12 heterodimer activity by the cofactor FHL2. Molecular and cellular biology 46 15509787
1998 Xenopus eHAND: a marker for the developing cardiovascular system of the embryo that is regulated by bone morphogenetic proteins. Mechanisms of development 45 9507100
2000 Early exclusion of hand1-deficient cells from distinct regions of the left ventricular myocardium in chimeric mouse embryos. Developmental biology 44 11076684
1998 Molecular cloning of the human Hand1 gene/cDNA and its tissue-restricted expression in cytotrophoblastic cells and heart. Gene 44 9931445
2002 HAND1 and HAND2 are expressed in the adult-rodent heart and are modulated during cardiac hypertrophy. Biochemical and biophysical research communications 42 12359233
2005 Analysis of Saccharomyces cerevisiae hexose carrier expression during wine fermentation: both low- and high-affinity Hxt transporters are expressed. FEMS yeast research 41 15691740
2005 MEF2-dependent recruitment of the HAND1 transcription factor results in synergistic activation of target promoters. The Journal of biological chemistry 39 16043483
2004 Role of Hand1/eHAND in the dorso-ventral patterning and interventricular septum formation in the embryonic heart. Molecular and cellular biology 39 15143159
1994 High-copy suppression of glucose transport defects by HXT4 and regulatory elements in the promoters of the HXT genes in Saccharomyces cerevisiae. Genetics 38 7982576
2010 Identification of Thymosin β4 as an effector of Hand1-mediated vascular development. Nature communications 35 20975697
2011 Functional dissection of the glucose signaling pathways that regulate the yeast glucose transporter gene (HXT) repressor Rgt1. Journal of cellular biochemistry 34 21748783
2011 Investigation of somatic NKX2-5, GATA4 and HAND1 mutations in patients with tetralogy of Fallot. Pathology 33 21519287
2020 HAND1 loss-of-function within the embryonic myocardium reveals survivable congenital cardiac defects and adult heart failure. Cardiovascular research 31 31286141
2012 A Phox2- and Hand2-dependent Hand1 cis-regulatory element reveals a unique gene dosage requirement for Hand2 during sympathetic neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience 31 22323723
2007 Biochemical evidence for glucose-independent induction of HXT expression in Saccharomyces cerevisiae. FEBS letters 31 17586499
2001 Human eHAND, but not dHAND, is down-regulated in cardiomyopathies. Journal of molecular and cellular cardiology 30 11549340
2014 Hand1 phosphoregulation within the distal arch neural crest is essential for craniofacial morphogenesis. Development (Cambridge, England) 29 25053435
2014 Elf5 counteracts precocious trophoblast differentiation by maintaining Sox2 and 3 and inhibiting Hand1 expression. Developmental biology 28 24859262
2011 Somatic mutations in NKX2–5, GATA4, and HAND1 are not a common cause of tetralogy of Fallot or hypoplastic left heart. American journal of medical genetics. Part A 28 22043484
2011 Eomesodermin, HAND1, and CSH1 proteins are induced by cellular stress in a stress-activated protein kinase-dependent manner. Molecular reproduction and development 26 21710638
2009 Overexpression of the transcription factor Hand1 causes predisposition towards arrhythmia in mice. Journal of molecular and cellular cardiology 26 19376125
2016 HAND1 loss-of-function mutation associated with familial dilated cardiomyopathy. Clinical chemistry and laboratory medicine 25 26581070
2006 Sox15 enhances trophoblast giant cell differentiation induced by Hand1 in mouse placenta. Differentiation; research in biological diversity 25 16759287
2019 Variation in a Left Ventricle-Specific Hand1 Enhancer Impairs GATA Transcription Factor Binding and Disrupts Conduction System Development and Function. Circulation research 24 31366290
2002 Hxt-carrier-mediated glucose efflux upon exposure of Saccharomyces cerevisiae to excess maltose. Applied and environmental microbiology 23 12200274
2021 HAND1 and BARX1 Act as Transcriptional and Anatomic Determinants of Malignancy in Gastrointestinal Stromal Tumor. Clinical cancer research : an official journal of the American Association for Cancer Research 22 33451979
2015 Hand1-Luc embryonic stem cell test (Hand1-Luc EST): a novel rapid and highly reproducible in vitro test for embryotoxicity by measuring cytotoxicity and differentiation toxicity using engineered mouse ES cells. The Journal of toxicological sciences 21 25786529
2014 Prenatal alcohol exposure causes the over-expression of DHAND and EHAND by increasing histone H3K14 acetylation in C57 BL/6 mice. Toxicology letters 21 24857828
2010 Analysis of a Hand1 hypomorphic allele reveals a critical threshold for embryonic viability. Developmental dynamics : an official publication of the American Association of Anatomists 21 20737509
2003 Expression and regulation of eHAND during limb development. Developmental dynamics : an official publication of the American Association of Anatomists 20 12666206
2021 Human HAND1 inhibits the conversion of cholesterol to steroids in trophoblasts. Journal of genetics and genomics = Yi chuan xue bao 19 34391879
2000 Negative regulation of selected bHLH proteins by eHAND. Experimental cell research 19 10837146
2021 Conditional Mutation of Hand1 in the Mouse Placenta Disrupts Placental Vascular Development Resulting in Fetal Loss in Both Early and Late Pregnancy. International journal of molecular sciences 18 34502440
2016 The Transcription Factor Hand1 Is Involved In Runx2-Ihh-Regulated Endochondral Ossification. PloS one 18 26918743
2014 MicroRNA-363 negatively regulates the left ventricular determining transcription factor HAND1 in human embryonic stem cell-derived cardiomyocytes. Stem cell research & therapy 18 24906886
2011 Two novel HAND1 mutations in Chinese patients with ventricular septal defect. Clinica chimica acta; international journal of clinical chemistry 18 22032825
2017 HAND1 loss-of-function mutation contributes to congenital double outlet right ventricle. International journal of molecular medicine 17 28112363
2010 A Tlx2-Cre mouse line uncovers essential roles for hand1 in extraembryonic and lateral mesoderm. Genesis (New York, N.Y. : 2000) 16 20506548
2023 The developmental regulator HAND1 inhibits gastric carcinogenesis through enhancing ER stress apoptosis via targeting CHOP and BAK which is augmented by cisplatin. International journal of biological sciences 14 36594085
2017 The HAND1 frameshift A126FS mutation does not cause hypoplastic left heart syndrome in mice. Cardiovascular research 14 29016838
2016 HAND1 Loss-of-Function Mutation Causes Tetralogy of Fallot. Pediatric cardiology 13 27942761
2002 A differential screen for putative targets of the bHLH transcription factor Hand1 in cardiac morphogenesis. Mechanisms of development 13 14516662
2021 Expression dynamics of HAND1/2 in in vitro human cardiomyocyte differentiation. Stem cell reports 12 34297940
2017 Defective Hand1 phosphoregulation uncovers essential roles for Hand1 in limb morphogenesis. Development (Cambridge, England) 12 28576769
2012 Assessment of technical protocols for novel embryonic stem cell tests with molecular markers (Hand1- and Cmya1-ESTs): a preliminary cross-laboratory performance analysis. The Journal of toxicological sciences 12 22863864
2023 HAND1 knockdown disrupts trophoblast global gene expression. Physiological reports 10 36695714
2021 Bmp Signaling Regulates Hand1 in a Dose-Dependent Manner during Heart Development. International journal of molecular sciences 10 34576009
2016 Prediction of in vivo developmental toxicity by combination of Hand1-Luc embryonic stem cell test and metabolic stability test with clarification of metabolically inapplicable candidates. Toxicology letters 10 27444379
2013 The basic helix-loop-helix transcription factor Hand1 regulates mouse development as a homodimer. Developmental biology 9 23911935
2025 Cardiomyocyte Foxp1-Specific Deletion Promotes Post-injury Heart Regeneration via Targeting Usp20-HIF1ɑ-Hand1 Signaling Pathway. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 39899693
2014 Nuclear translocation of Hand-1 acts as a molecular switch to regulate vascular radiosensitivity in medulloblastoma tumors: the protein uPAR is a cytoplasmic sequestration factor for Hand-1. Molecular cancer therapeutics 8 24623737
2003 Expression of the human Hand1 gene in trophoblastic cells is transcriptionally regulated by activating and repressing specificity protein (Sp)-elements. Gene 8 12527202
2024 Circulating-tumour DNA methylation of HAND1 gene: a promising biomarker in early detection of colorectal cancer. BMC medical genomics 7 38689296
2020 The Transcription Factor HAND1 Is Involved in Cortical Bone Mass through the Regulation of Collagen Expression. International journal of molecular sciences 7 33207791
2024 Novel and deleterious nucleotide variations in the HAND1 gene probably affect miRNA target sites and protein function in pediatric patients with congenital heart disease. Molecular biology reports 6 38551686
2022 MiRNA-196-5p Promotes Proliferation and Migration in Cholangiocarcinoma via HAND1/Wnt/β-Catenin Signaling Pathway. Journal of oncology 6 35466323
2016 Hand1 overexpression inhibits medulloblastoma metastasis. Biochemical and biophysical research communications 6 27297109
2014 Hearty miR-363 controls HAND1 in cardiac cell specification. Stem cell research & therapy 5 25157599
2002 A differential screen for putative targets of the bHLH transcription factor Hand1 in cardiac morphogenesis. Gene expression patterns : GEP 5 12617838
2002 Evidence for involvement of Saccharomyces cerevisiae protein kinase C in glucose induction of HXT genes and derepression of SUC2. FEMS yeast research 5 12702297
2020 Analyses of DNA double-strand break repair pathways in tandem arrays of HXT genes of Saccharomyces cerevisiae. Journal of microbiology (Seoul, Korea) 4 33125670
2020 Optimising recruitment to the HAND-1 RCT feasibility study: integration of the QuinteT Recruitment Intervention (QRI). Pilot and feasibility studies 4 33292646
2021 Deletion of a Hand1 lncRNA-Containing Septum Transversum Enhancer Alters lncRNA Expression but Is Not Required for Hand1 Expression. Journal of cardiovascular development and disease 3 34064373
2017 Asymmetrically reduced expression of hand1 homeologs involving a single nucleotide substitution in a cis-regulatory element. Developmental biology 3 28359808
2025 HAND1 level controls the specification of multipotent cardiac and extraembryonic progenitors from human pluripotent stem cells. The EMBO journal 2 40164946
2024 Vitamin C inactivates c-Jun N-terminal kinase to stabilize heart and neural crest derivatives expressed 1 (Hand1) in regulating placentation and maintenance of pregnancy. Cellular and molecular life sciences : CMLS 2 39008099
2011 Sequence variations of NKX2-5 and HAND1 genes in patients with atrial isomerism. Anadolu kardiyoloji dergisi : AKD = the Anatolian journal of cardiology 2 21561848
2025 HAND1, partially mediated through ape-specific LTR binding, is essential for human extra-embryonic mesenchyme derivation from iPSCs. Cell reports 1 40220298
2024 Novel high throughput screen reports that benzo(a)pyrene overrides mouse trophoblast stem cell multipotency, inducing SAPK activity, HAND1 and differentiated trophoblast giant cells. Placenta 1 38245404
2024 The generation and validation of a dual cardiac HAND1-Tomato NKX2-5-GFP human embryonic stem cell line UMANe002-A-3. Stem cell research 1 38460234
2024 Identification and functional validation of variants in the promoter region of HAND1 gene in sporadic tetralogy of Fallot. Pediatric research 1 39537763
2022 Adgrg1 is a new transcriptional target of Hand1 during trophoblast giant cell differentiation. Journal of reproductive immunology 1 36228547
2017 [Identification and functional analysis of 
a novel HAND1 mutation associated with congenital ventricular septal defect]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 1 29317578
2007 Constitutive over-expression of VEGF results in reduced expression of Hand-1 during cardiac development in Xenopus. Biochemical and biophysical research communications 1 17544370