Affinage

HOXA1

Homeobox protein Hox-A1 · UniProt P49639

Length
335 aa
Mass
36.7 kDa
Annotated
2026-06-10
100 papers in source corpus 42 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXA1 is a homeodomain transcription factor that acts at the top of the developmental cascade specifying hindbrain rhombomere identity, in which its loss eliminates rhombomeres 4 and 5, abolishes facial and abducens motor neurons, and disrupts neural crest migration (PMID:8287791, PMID:7903632). It establishes rhombomere identity by directly regulating the rhombomere-patterning gene network, initiating and maintaining Hoxb1 expression in rhombomere 4 through auto- and para-regulatory interactions and activating the r4 marker EphA2/Eck by binding Hox-Pbx consensus sites cooperatively with PBX1 (PMID:7956823, PMID:9733765, PMID:9463349, PMID:9463359). This cooperative DNA binding requires the YPWM hexapeptide motif, which contacts the PBX homeodomain (PMID:9582372). HOXA1 expression is itself a direct retinoic acid response: RARgamma mediates RA induction (PMID:8105479, PMID:8650243), and a 3' RARE drives correct caudal and boundary expression in vivo, with mutation of this element phenocopying a partial knockout (PMID:7743939, PMID:9053316). Beyond its r4-specifying role, HOXA1 is required cell-autonomously for neural crest generation, cardiac neural crest specification and cardiovascular morphogenesis, inner ear development, and RA-driven neuronal differentiation of ES cells, governing target cascades that include Zic1, Hnf1b, Foxd3, Pax8, and Fgfr3 (PMID:11532923, PMID:21940751, PMID:20171203, PMID:18512762, PMID:21784065). Genome-wide binding studies show HOXA1 reciprocally cross-regulates the pluripotency factor Nanog and targets multiple components of the Wnt, TGF-beta, Hedgehog, and Hippo pathways, functioning as a switch between pluripotency and differentiation (PMID:28584089, PMID:28982536). In pathological contexts HOXA1 acts as an oncogene: it transcriptionally upregulates Bcl-2, PRLR, and glycolytic enzymes ENO1 and PGK1, drives GRB2/MEK1-dependent MAPK signaling, and engages a non-transcriptional route through RBCK1/HOIL-1 and TRAF2 to activate NF-kappaB upstream of IkappaB, with both the YPWM motif and NF-kappaB activation required for transformation (PMID:12482855, PMID:21957483, PMID:23064471, PMID:27382069, PMID:37286120). Its locus is heavily controlled by chromatin and epigenetic inputs, including KDM3A/KDM3B H3K9 demethylation (the former activated by ACK1 phosphorylation), PRC2/SUZ12 H3K27me3, lncRNA-directed methylation, and a distal enhancer engaged through long-range chromatin looping (PMID:17663992, PMID:22020899, PMID:25148682, PMID:31147716).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Established the core developmental requirement for HOXA1 by showing it is needed to build the posterior hindbrain, defining the process the gene controls.

    Evidence Targeted knockout in mice with 3D reconstruction and neurofilament immunostaining, plus in situ analysis of downstream patterning genes

    PMID:7903632 PMID:8287791

    Open questions at the time
    • Did not identify the direct transcriptional targets responsible for r4/r5 loss
    • Did not distinguish cell-autonomous from non-autonomous effects
  2. 1993 High

    Identified RARgamma and a 3' RARE as the upstream signal driving HOXA1, answering how positional retinoic acid information is converted into Hoxa1 transcription.

    Evidence RARgamma allelic disruption in F9 cells and transgenic reporter/Cre-loxP mutagenesis of the 3' RARE in mice

    PMID:7743939 PMID:8105479 PMID:9053316

    Open questions at the time
    • Additional enhancers beyond the 3' RARE not fully mapped at this stage
    • Did not address chromatin context of RARE activation
  3. 1994 High

    Demonstrated HOXA1 acts as a transcriptional determinant of rhombomere identity by showing ectopic expression imposes r4-like fate and induces Hoxb1.

    Evidence Gain-of-function transgenic mice with Hoxb1/lacZ dual reporter and in situ hybridization, with zebrafish RNA injection phenocopying RA

    PMID:7956823 PMID:8631251

    Open questions at the time
    • Did not show direct binding of HOXA1 to the Hoxb1 enhancer
    • Mechanism of fate transformation not resolved
  4. 1998 High

    Defined the molecular logic of HOXA1 target activation, showing cooperative PBX1 binding via the YPWM motif and direct regulation of EphA2 and Hoxb1 in r4.

    Evidence EMSA, reporter transactivation, hexapeptide/homeodomain mutagenesis, transgenic enhancer assays and Hoxa1/Hoxb1 double-mutant analysis

    PMID:9463349 PMID:9463359 PMID:9582372 PMID:9733765

    Open questions at the time
    • Genome-wide direct target repertoire still unknown at this stage
    • Did not establish how monomer vs heterodimer binding choices are made in vivo
  5. 2001 High

    Refined HOXA1 functional specificity by mapping activity to homeodomain residues and the N-terminal activation domain and showing cell-autonomous requirement for neural crest generation.

    Evidence Domain-swap and homeodomain mutagenesis reporter assays, SOX/OCT site transgenics, and wild-type cell grafting into double-mutant embryos

    PMID:11278854 PMID:11466434 PMID:11532923 PMID:12060683

    Open questions at the time
    • How HOXA1 and HOXB1 achieve distinct activities in vivo despite shared targets
    • Mechanism of apoptotic/circuit repression in null mice not molecularly defined
  6. 2002 High

    Extended HOXA1 function to cardiovascular and broader developmental programs and uncovered its oncogenic activity through Bcl-2-mediated survival.

    Evidence Hoxa1-IRES-Cre lineage tracing and null cardiovascular phenotyping; forced expression/siRNA and soft-agar transformation in mammary cells

    PMID:12482855 PMID:20171203 PMID:21940751

    Open questions at the time
    • Direct cardiac NCC target genes not all defined
    • Oncogenic target network beyond Bcl-2 not yet mapped
  7. 2007 Medium

    Built out the oncogenic effector network and showed dynamic RA/PcG epigenetic control of the HOXA1 locus.

    Evidence Microarray profiling, MEK1 inhibitor epistasis, E-cadherin/Rac1 perturbation in mammary cells, and time-resolved ChIP at the Hoxa1 RARE

    PMID:16373333 PMID:17213808 PMID:17663992

    Open questions at the time
    • Direct vs indirect status of GRB2/MEK1/SDFR1 induction not fully resolved
    • Single-lab cancer cell line context limits generality
  8. 2011 Medium

    Defined epigenetic activators of HOXA1 and expanded its developmental target catalog and fate map.

    Evidence KDM3A siRNA and H3K9me2 ChIP at the promoter, microdissected r3-r5 microarray, Hoxa1-IRES-Cre fate mapping, and hexapeptide mutagenesis in cancer cells

    PMID:20171203 PMID:21784065 PMID:21957483 PMID:22020899

    Open questions at the time
    • Whether developmental targets are direct binding events not all tested
    • Link between KDM3A regulation and physiological HOXA1 contexts unclear
  9. 2014 High

    Connected upstream kinase signaling to HOXA1 epigenetic activation, showing ACK1 phosphorylates KDM3A to relieve H3K9me2 repression.

    Evidence In vitro kinase assay, histone-mark ChIP, and ACK1 inhibitor (AIM-100/Dasatinib) treatment in breast cancer cells

    PMID:25148682

    Open questions at the time
    • Single-lab data; physiological relevance beyond breast cancer untested
    • Other KDM3A substrate/locus consequences not addressed
  10. 2016 High

    Revealed a non-transcriptional signaling function for HOXA1, showing it binds RBCK1 and TRAF2 to activate NF-kappaB upstream of IkappaB.

    Evidence Proteome-wide interaction screen, Co-IP, domain-deletion mutagenesis, NF-kappaB reporter assays and RBCK1/TRAF2 epistasis

    PMID:27382069

    Open questions at the time
    • Single-lab Co-IP without reciprocal in vivo validation
    • Subcellular site of HOXA1-NF-kappaB activation not fully resolved
  11. 2017 High

    Mapped HOXA1 genome-wide binding, establishing it as a regulator of pluripotency (mutual repression with Nanog) and multiple signaling pathways during differentiation.

    Evidence Hoxa1 and Nanog ChIP-seq in RA-differentiated ES cells, gain/loss transcriptomics in mouse and zebrafish, and in vivo enhancer reporter validation

    PMID:28584089 PMID:28982536

    Open questions at the time
    • Which binding events are functionally driving vs bystander not fully separated
    • Direct cofactor requirements at genome-wide sites not defined
  12. 2019 High

    Resolved long-range cis-regulation of HOXA1 by demonstrating a ~450 kb distal enhancer engages the promoter via chromatin looping to enable RA-induced expression and differentiation.

    Evidence CRISPR enhancer deletion, 3C chromatin loop analysis, rescue transcriptomics, and Hoxa1 ChIP at rescued gene promoters

    PMID:31147716

    Open questions at the time
    • Only ~18% of rescued gene promoters were directly bound, leaving indirect mechanisms unexplained
    • Single-lab ES-cell context
  13. 2023 Medium

    Extended HOXA1 oncogenic and pathological transcriptional output to vascular inflammation and tumor metabolism via direct activation of RelA/KLF4 and ENO1/PGK1.

    Evidence AAV-shHOXA1 in ApoE-/- atherosclerosis mice with ChIP, and reporter/knockdown/xenograft assays in cervical cancer

    PMID:37286120 PMID:37528397

    Open questions at the time
    • Single-lab disease-model findings not independently replicated
    • Whether these targets are context-specific or general HOXA1 targets unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HOXA1's dual roles as a positional developmental transcription factor and a non-transcriptional NF-kappaB activator are integrated, and what determines its switch between developmental and oncogenic target programs, remains unresolved.
  • No structural model of HOXA1-PBX1 on its in vivo enhancers
  • Mechanism selecting transcriptional vs cytoplasmic signaling functions unknown
  • Direct human Mendelian phenotype not established in this corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 6 GO:0003677 DNA binding 4 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2
Pathway
R-HSA-4839726 Chromatin organization 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
PBX1RBCK1TRAF2

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 Hoxa1 null mice display loss of rhombomeres 4 and 5, absence of facial and abducens motor neurons, and abnormal neural crest migration, establishing Hoxa1 as required for specification of rhombomere identity in the developing hindbrain. Targeted gene knockout in mice with 3D reconstructions, histological analysis, and whole-mount anti-neurofilament immunostaining Development High 7903632 8287791
1993 In Hoxa1 null mice, the expression of Krox-20, int-2/fgf-3, and Hoxb1 is aberrant, indicating that Hoxa1 is required upstream of these rhombomere-identity genes and for proper specification of r3–r8 cell identity and/or cell migration. In situ hybridization and carbocyanine dye injection tract tracing in Hoxa1 null mice Development High 7903632
1993 RAR-gamma mediates retinoic acid induction of Hoxa1 in F9 embryonal carcinoma cells; targeted disruption of RARgamma abolishes RA-induced Hoxa1 expression, establishing RARgamma as the primary receptor mediating this response in this cell context. Gene disruption of both RARgamma alleles in F9 cells followed by RA treatment and gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 8105479 8650243
1995 A retinoic acid response element (RARE) within the Hoxa1 3' enhancer is required for expression in neuroepithelium caudal to rhombomere 4; point mutations in the RARE abolish this expression domain in transgenic mice, demonstrating direct RA-mediated transcriptional control of Hoxa1. Transgenic mouse reporter assays with point mutations in the RARE; in vivo enhancer analysis Development High 7743939 9053316
1997 Mutation of the Hoxa1 3' RARE by Cre-loxP targeting reduces early Hoxa1 expression boundary establishment, causing rhombomere and cranial nerve abnormalities similar to (but milder than) the Hoxa1 total knockout, and abolishes correct Hoxa2 expression in rhombomere 5, demonstrating that this RARE directly mediates RA-driven Hoxa1 patterning function. Cre-loxP targeted mutation of the 3'RARE in mice; phenotypic analysis of neural and cranial structures Development High 9053316
1994 Ectopic widespread expression of Hoxa1 in transgenic mice induces ectopic Hoxb1 expression in rhombomere 2 and transforms select hindbrain regions toward rhombomere-4-like identity, demonstrating that Hoxa1 functions as a transcriptional regulator of Hoxb1 and a determinant of rhombomere identity. Beta-actin promoter-driven Hoxa1 transgenic mice with in situ hybridization; dual-transgenic reporter assay with Hoxb1/lacZ Development High 7956823
1996 Overexpression of Hoxa1 mRNA in zebrafish phenocopies retinoic acid treatment, causing anterior hindbrain abnormalities, duplication of Mauthner neurons in r2, and fate changes in r2 neural crest, establishing Hoxa1 as a mediator of RA-induced anterior hindbrain patterning. Synthetic RNA injection into fertilized zebrafish eggs; exogenous RA treatment with in situ hybridization Development Medium 8631251
1998 HOXA1 (and HOXB1), together with Pbx1, bind to Hox-Pbx consensus sites in the EphA2 (Eck) enhancer and co-expression of HOXA1 or HOXB1 with Pbx1 transactivates EphA2 enhancer-dependent reporter expression in vitro; EphA2 expression is reduced in hoxa1/hoxb1 double mutant mice, establishing EphA2 as a direct transcriptional target of Hoxa1 in rhombomere 4. In vitro DNA binding assays (EMSA), reporter gene transactivation assays, transgenic mouse enhancer analysis, and analysis of double-mutant mice The Journal of biological chemistry High 9733765
1998 Genetic analysis of Hoxa1/Hoxb1 double-null mice reveals that both genes cooperate to establish and maintain Hoxb1 expression in rhombomere 4 via auto- and para-regulatory interactions, and that the EphA2 r4 marker fails to activate in double mutants, indicating that Hoxa1 and Hoxb1 are required to initiate r4 specification. Genetic double-mutant analysis; in situ hybridization for rhombomere markers including Eph receptors Development High 9463349 9463359
1998 The YPWM hexapeptide motif of HOXA1 is strictly required for cooperative DNA binding with PBX1 in vitro and for cooperative interaction in vivo; the GKFQ domain of PBX increases DNA binding by PBX but is not the primary contact for the HOXA1 YPWM motif; the YPWM motif contacts the PBX homeodomain. In vitro binding assays (EMSA), reporter gene assays, truncated and mutant PBX/HOX protein analysis The Journal of biological chemistry High 9582372
1998 Hoxa1 and Hoxb1 synergize in patterning the facial (VII) through accessory (XI) cranial nerves and the second pharyngeal arch; combined loss results in involution of the second arch by E10.5, complete loss of second arch-derived structures, and external/middle ear development disruption, revealing extensive functional synergy not apparent from single mutants. Compound Hoxa1/Hoxb1 null mouse mutant analysis; neurofilament staining; retrograde motor neuron labeling; neural crest marker analysis Development High 10529420 9463359
2001 HOXB1 has significantly higher transcriptional activity than its paralog HOXA1 on the Hoxb1 auto-regulatory enhancer (b1-ARE) in embryonal carcinoma cells; this differential activity maps to the N-terminal transcriptional activation domain of HOXB1; in vivo, Hoxa1 is the primary mediator of the RA response at the b1-ARE in a SOX/OCT heterodimer-dependent manner. Reporter gene assays in embryonal carcinoma cells; domain-swap analysis; transgenic mouse analysis with SOX/OCT site mutations; Hoxa1 mutant mice The Journal of biological chemistry High 11278854
2001 Loss of Hoxa1 results in reduction of rhombomere 4 size and loss of its ability to generate neural crest cells, demonstrated to be cell-autonomous by grafting wild-type cells into double-mutant mouse embryo cultures. Ectoderm-specific Hoxb1 regulatory mutation combined with Hoxa1 null; molecular/lineage analysis; in vitro grafting experiments Development High 11532923
2001 In Hoxa1 null mice, ectopic neuronal groups originating from misspecified r3-r4 levels escape apoptosis, establish a supernumerary neuronal circuit with r2 identity, and become functionally integrated into the respiratory rhythm-generating network postnatally, demonstrating that Hoxa1 normally represses this alternate neural circuit. Electrophysiological recording, anatomical analysis, molecular identity marker expression in Hoxa1 null mice The Journal of neuroscience Medium 11466434
2002 Homeodomain residues 2 and 3 (Asn and Ala) of Hoxa1 determine its functional specificity on the somatostatin TSEII enhancer as a monomer, but do not affect activity in HOXA1-Pbx1 heterodimers; on the Hoxb1 b1-ARE, these residues can modulate activity in a cell-type dependent manner even in the presence of Pbx. Site-directed mutagenesis of homeodomain residues; reporter gene transactivation assays in multiple cell lines with defined cofactors Nucleic acids research Medium 12060683
2002 Hoxa1 is required upstream of several genes regulating cardiac neural crest cell specification; Hoxa1 null mice exhibit cardiovascular malformations (interrupted aortic arch, aberrant subclavian artery, Tetralogy of Fallot), and lineage tracing shows Hoxa1 is expressed in cardiac NCC precursors. Hoxa1-IRES-Cre lineage tracing; Hoxa1 null mouse cardiovascular phenotyping; molecular marker analysis for NCC specification genes Human molecular genetics High 20171203 21940751
2002 HOXA1 transcriptionally upregulates Bcl-2, promoting cell survival in human mammary carcinoma cells; forced HOXA1 expression also promotes anchorage-independent proliferation and induces oncogenic transformation of immortalized mammary epithelial cells in a Bcl-2-dependent manner. Forced expression and siRNA knockdown of HOXA1 in human mammary carcinoma cells; luciferase reporter assays; soft-agar colony formation; in vivo tumor formation The Journal of biological chemistry Medium 12482855
2005 E-cadherin-dependent signaling via Rac1 increases HOXA1 expression at confluence in mammary carcinoma cells, and this HOXA1 upregulation is required for E-cadherin-dependent anchorage-independent proliferation and survival. E-cadherin function-blocking antibody, Ca2+ chelation with EGTA, Rac1 pathway analysis, HOXA1 forced expression and siRNA in MCF-7 cells The Journal of biological chemistry Medium 16373333
2007 HOXA1-stimulated oncogenicity in human mammary carcinoma cells is mediated by transcriptional upregulation of GRB2, MEK1, and SDFR1, leading to increased p44/42 MAP kinase phosphorylation and activity; MEK1 inhibitor abolishes HOXA1-mediated proliferation, survival, and transformation. Microarray gene expression profiling; Western blot for phospho-MAPK; MEK1 inhibitor treatment; forced HOXA1 expression and siRNA knockdown Oncogene Medium 17213808
2007 RARgamma and RXRalpha are constitutively associated with the Hoxa1 RARE; upon RA treatment, pCIP, p300, and RNA Pol II increase at the Hoxa1 RARE while the PcG protein SUZ12 dissociates; H3K27me3 decreases while H3ac and H3K4me2 remain constant; upon RA removal, SUZ12 re-associates, revealing dynamic epigenetic regulation of Hoxa1 by RA signaling and PcG repression. Chromatin immunoprecipitation (ChIP) assays in F9 embryonal carcinoma cells for RAR, RXR, co-activators, Pol II, SUZ12, and histone modifications Journal of molecular biology Medium 17663992
2008 Hoxa1 is required for neuronal differentiation of ES cells along the neural lineage in response to RA; Hoxa1 null ES cells fail to express neuronal markers and instead upregulate endodermal markers; re-introduction of Hoxa1 rescues neuronal differentiation; Hoxa1 may act partly by inhibiting Sox17 expression. Hoxa1 null ES cell differentiation assay; RA-induced embryoid body protocol; re-expression of exogenous Hoxa1 under metallothionein promoter; Sox17 overexpression in WT ES cells Journal of neuroscience research Medium 18512762
2011 KDM3A (JMJD1A) activates HOXA1 transcription by demethylating histone H3K9me2 at the HOXA1 promoter; KDM3A knockdown decreases HOXA1 and CCND1 expression and causes G1 arrest; KDM3A and HOXA1 expression levels are statistically correlated in cancer cell lines and bladder cancer samples. siRNA knockdown of KDM3A; ChIP for H3K9me2 at HOXA1 promoter; gene expression analysis; cell proliferation assays International journal of cancer Medium 22020899
2011 Hoxa1 null microarray analysis identifies ~300 downstream targets in the r3-r5 hindbrain region; validated targets include neural crest specification genes Zic1, Hnf1b, Foxd3 (downregulated in cardiac NCC-generating hindbrain), and inner ear genes Pax8 and Fgfr3, establishing Hoxa1 as an upstream regulator in these developmental cascades. Microarray analysis on laser-microdissected r3-r5 tissue from Hoxa1 null vs. wild-type embryos; RT-PCR validation Developmental biology Medium 21784065
2011 Hoxa1 lineage tracing via Hoxa1-IRES-Cre reveals Hoxa1-expressing precursors contribute to rhombomere 3 (more anterior than previously reported), otic epithelium (excluding sensory patches), atria, and cardiac outflow tract, indicating a direct role for Hoxa1 in these tissues. Genetic lineage tracing using Hoxa1-IRES-Cre knock-in mouse line with Rosa26-reporter Developmental biology High 20171203
2011 The Pbx-interaction hexapeptide (YPWM-containing) motif of Hoxa1 is essential for its oncogenic activity; a Hoxa1 mutant with substituted hexapeptide residues loses the ability to stimulate cell proliferation, anchorage-independent growth, and contact inhibition bypass. Site-directed mutagenesis of the hexapeptide; forced expression of wild-type vs. mutant Hoxa1 in mammary carcinoma cells; proliferation, soft-agar, and contact inhibition assays PloS one Medium 21957483
2012 A proteome-wide yeast two-hybrid screen and affinity co-purification identified 59 Hoxa1 interactors (45 confirmed by co-purification), including cell-signaling, cell-adhesion, and vesicular trafficking proteins; bimolecular fluorescence complementation revealed distinctive subcellular patterns (vesicular, cytoplasmic, or nuclear) for different interaction subsets. Yeast two-hybrid screening of ~12,200 ORF-derived polypeptides; affinity co-purification in animal cell lines; bimolecular fluorescence complementation BMC developmental biology Medium 23088713
2012 HOXA1 increases PRLR (prolactin receptor) mRNA and protein expression in MCF-7 cells; forced HOXA1 expression enhances prolactin-stimulated phosphorylation of STAT5A/B and p44/42 MAPK and enhances hPRL-stimulated cell proliferation and anchorage-independent growth, which is blocked by a PRLR antagonist, establishing PRLR as a functional downstream effector of HOXA1 oncogenicity. Forced HOXA1 expression in MCF-7 cells; PRLR mRNA/protein quantification; phosphorylation assays; PRLR antagonist; soft-agar growth assay International journal of oncology Medium 23064471
2014 ACK1 tyrosine kinase phosphorylates the H3K9 demethylase KDM3A at Tyr-1114 in response to heregulin, decreasing H3K9me2 deposition and thereby activating HOXA1 transcription; ACK1 inhibition by AIM-100 or Dasatinib restores H3K9me2 marks and suppresses HOXA1 expression, even in tamoxifen-resistant conditions. Kinase assay demonstrating ACK1 phosphorylation of KDM3A; histone methylation ChIP; gene expression analysis; ACK1 small molecule inhibitors in breast cancer cells The Journal of biological chemistry High 25148682
2015 lncRNA HOTAIRM1 sequesters histone methyltransferases G9a (H3K9me2) and EZH2 (H3K27me3) and DNA methyltransferases (DNMT1, DNMT3b) away from the HOXA1 gene TSS, causing demethylation of H3K9 and H3K27 and reduced DNA methylation, thereby activating HOXA1 transcription in glioblastoma cells. Chromatin immunoprecipitation (ChIP); RNA-ChIP; bisulfite sequencing methylation analysis; siRNA knockdown of HOTAIRM1 Journal of experimental & clinical cancer research Medium 30376874
2015 YAP (Hippo pathway transcriptional co-activator) regulates Hoxa1 expression in dental/oral epithelium and skin epidermis; ChIP assay suggests YAP acts through TEAD transcription factors to activate Hoxa1; Hoxa1 is functionally involved in YAP-regulated epithelial progenitor cell proliferation by sphere formation assay. Yap conditional knockout and YAP transgenic mice; RNA-Seq; ChIP for YAP/TEAD; sphere formation assay; in situ hybridization Molecular and cellular biology Medium 25691658
2016 HOXA1 binds RBCK1/HOIL-1 and TRAF2 (TNF receptor-associated proteins) via its 11-histidine repeat and homeodomain; HOXA1 activates NF-κB in a non-transcriptional manner, acting upstream of the NF-κB inhibitor IκB; epistasis experiments show RBCK1 and TRAF2 effects on NF-κB are epistatic to HOXA1; NF-κB activation is required for HOXA1 oncogenic activity. Proteome-wide interaction screening; co-immunoprecipitation; reporter assays for NF-κB activity; domain-deletion mutagenesis; epistasis analysis with RBCK1/TRAF2 knockdown Nucleic acids research High 27382069
2017 Genome-wide Hoxa1 ChIP-seq in RA-differentiated ES cells reveals dynamic binding to pluripotency regulatory targets; Hoxa1 co-occupies many sites with Nanog, including the Nanog promoter itself; Nanog binds a 3' enhancer of Hoxa1; mutual repression between Hoxa1 and Nanog provides a molecular switch between pluripotency and differentiation. Hoxa1 also binds regulatory regions of Sox2, Esrrb, and Myc. Genome-wide ChIP-seq for Hoxa1 and Nanog in RA-treated ES cells; gene expression analysis at multiple differentiation time-points Proceedings of the National Academy of Sciences of the United States of America High 28584089
2017 Genome-wide Hoxa1 ChIP-seq combined with differential gene expression in Hoxa1 gain- and loss-of-function mouse/zebrafish embryos identifies Hoxa1 as a regulator of multiple developmental signaling pathways (Wnt, TGF-β, Hedgehog, Hippo) by targeting multiple components within each pathway; two validated enhancers (in Dok5 and Wls1) mediate neural expression in vivo. Hoxa1 ChIP-seq in RA-differentiated mouse ES cells; microarray differential expression in Hoxa1 gain/loss-of-function mouse and zebrafish; in vivo transgenic enhancer reporter assays Developmental biology High 28982536
2017 KDM3B binds to the retinoic acid response element (RARE) of the HOXA1 gene (but not its promoter) and regulates HOXA1 expression; KDM3B knockdown increases H3K9me1 but decreases H3K9me2 at the RARE, modulating HOXA1 transcription in AML cells. ChIP for KDM3B and histone marks (H3K9me1, H3K9me2) at HOXA1 RARE; siRNA knockdown; Western blot; real-time PCR Leukemia & lymphoma Medium 28540746
2019 A distal enhancer ~450 kb from the Hoxa1 locus interacts with the Hoxa1 promoter via a long-range chromatin loop; deletion of this enhancer significantly inhibits RA-induced Hoxa1 expression and blocks early ES cell differentiation; restoration of Hoxa1 expression rescues ~40% of differentially expressed genes, and ~18% of rescued gene promoters are directly bound by Hoxa1. CRISPR/Cas9 enhancer deletion; 3C/chromatin loop analysis; transcriptome analysis; ChIP for Hoxa1 binding at rescued gene promoters Nucleic acids research High 31147716
2020 lncRNA HOTAIRM1 prevents PRC2 complex (EZH2/SUZ12) binding at the HOXA1 promoter, inhibiting H3K27me3 deposition and thereby maintaining HOXA1 expression; HOTAIRM1 knockdown increases H3K27me3 at the HOXA1 promoter and reduces HOXA1 expression in tamoxifen-resistant MCF-7 cells. ChIP for EZH2, SUZ12, and H3K27me3 at HOXA1 promoter; HOTAIRM1 knockdown; RNA-immunoprecipitation for HOTAIRM1-EZH2 interaction Journal of Cancer Medium 32284737
2023 HOXA1 transcriptionally activates NF-κB RelA (p65) and KLF4 in vascular smooth muscle cells (VSMCs), promoting lipid accumulation, VSMC-to-macrophage phenotypic switching, and inflammation; HOXA1 knockdown via AAV1-shHOXA1 reduces atherosclerotic plaque formation in ApoE-/- mice. AAV-mediated shRNA knockdown of HOXA1 in ApoE-/- atherosclerosis mice; in vitro POV-PC-treated VSMC model; Western blot; ChIP for HOXA1 at RelA and KLF4 promoters Molecular medicine Medium 37528397
2023 HOXA1 directly regulates the transcriptional activity of ENO1 and PGK1 (glycolytic enzymes), promoting aerobic glycolysis and cancer progression in cervical cancer cells; HOXA1 knockdown reduces glycolysis and tumor growth in vivo. Luciferase reporter assays with ENO1/PGK1 promoters; HOXA1 overexpression and knockdown in cervical cancer cells; in vivo xenograft model with glycolysis metabolite measurement Cellular signalling Medium 37286120
2015 HOTAIR lncRNA promotes chemoresistance in SCLC by recruiting DNMT1 and DNMT3b to methylate the HOXA1 gene promoter; HOTAIR knockdown reduces HOXA1 methylation and restores HOXA1 expression; RNA immunoprecipitation confirmed a direct interaction between HOTAIR RNA and HOXA1 locus. Bisulfite sequencing PCR; Western blot for DNMTs; RNA immunoprecipitation; HOTAIR siRNA knockdown in resistant SCLC cells Laboratory investigation Medium 26707824
2005 Polyhistidine tract expansions in HOXA1 isoform A (11 and 12 histidines) cause protein aggregation in the nucleus and increased cell death compared to normal (10) or shorter variants; aggregates are ubiquitinated and inhibited by the histidine-modifying compound DEPC. Forced expression of HOXA1 polyhistidine variants in COS-7 and SK-N-SH cells; immunofluorescence for aggregation; DEPC treatment; cell viability assays Biochemical and biophysical research communications Medium 16168961

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Two rhombomeres are altered in Hoxa-1 mutant mice. Development (Cambridge, England) 362 8287791
1993 Loss of Hox-A1 (Hox-1.6) function results in the reorganization of the murine hindbrain. Development (Cambridge, England) 309 7903632
1997 In vivo functional analysis of the Hoxa-1 3' retinoic acid response element (3'RARE). Development (Cambridge, England) 289 9053316
1998 Hoxa1 and Hoxb1 synergize in patterning the hindbrain, cranial nerves and second pharyngeal arch. Development (Cambridge, England) 261 9463359
1998 Genetic interactions between Hoxa1 and Hoxb1 reveal new roles in regulation of early hindbrain patterning. Development (Cambridge, England) 252 9463349
2005 Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nature genetics 214 16155570
1995 Evolutionary-conserved enhancers direct region-specific expression of the murine Hoxa-1 and Hoxa-2 loci in both mice and Drosophila. Development (Cambridge, England) 185 7743939
1999 Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development (Cambridge, England) 163 10529420
1996 Ectopic expression of Hoxa-1 in the zebrafish alters the fate of the mandibular arch neural crest and phenocopies a retinoic acid-induced phenotype. Development (Cambridge, England) 162 8631251
1994 Ectopic Hoxa-1 induces rhombomere transformation in mouse hindbrain. Development (Cambridge, England) 152 7956823
1993 Loss of retinoic acid receptor gamma function in F9 cells by gene disruption results in aberrant Hoxa-1 expression and differentiation upon retinoic acid treatment. Proceedings of the National Academy of Sciences of the United States of America 150 8105479
2000 Roles of Hoxa1 and Hoxa2 in patterning the early hindbrain of the mouse. Development (Cambridge, England) 141 10662633
2018 Over-expressed lncRNA HOTAIRM1 promotes tumor growth and invasion through up-regulating HOXA1 and sequestering G9a/EZH2/Dnmts away from the HOXA1 gene in glioblastoma multiforme. Journal of experimental & clinical cancer research : CR 138 30376874
2002 Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. The Journal of biological chemistry 127 12482855
2007 Retinoid regulated association of transcriptional co-regulators and the polycomb group protein SUZ12 with the retinoic acid response elements of Hoxa1, RARbeta(2), and Cyp26A1 in F9 embryonal carcinoma cells. Journal of molecular biology 112 17663992
2013 linc-HOXA1 is a noncoding RNA that represses Hoxa1 transcription in cis. Genes & development 111 23723417
2000 Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology 110 11091361
1996 Cell-type and promoter-context dependent retinoic acid receptor (RAR) redundancies for RAR beta 2 and Hoxa-1 activation in F9 and P19 cells can be artefactually generated by gene knockouts. Proceedings of the National Academy of Sciences of the United States of America 105 8650243
2014 Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100. European journal of cancer (Oxford, England : 1990) 103 24559685
2018 Long Non-Coding RNA HOXA Transcript Antisense RNA Myeloid-Specific 1-HOXA1 Axis Downregulates the Immunosuppressive Activity of Myeloid-Derived Suppressor Cells in Lung Cancer. Frontiers in immunology 97 29662483
1995 Regulation of the Xenopus labial homeodomain genes, HoxA1 and HoxD1: activation by retinoids and peptide growth factors. Developmental biology 97 7851655
2015 Long noncoding RNA-HOTAIR affects chemoresistance by regulating HOXA1 methylation in small cell lung cancer cells. Laboratory investigation; a journal of technical methods and pathology 94 26707824
2012 MicroRNA-10a is overexpressed in human pancreatic cancer and involved in its invasiveness partially via suppression of the HOXA1 gene. Annals of surgical oncology 94 22407312
2003 Neuronal defects in the hindbrain of Hoxa1, Hoxb1 and Hoxb2 mutants reflect regulatory interactions among these Hox genes. Development (Cambridge, England) 94 14522873
1998 An enhancer element in the EphA2 (Eck) gene sufficient for rhombomere-specific expression is activated by HOXA1 and HOXB1 homeobox proteins. The Journal of biological chemistry 91 9733765
2001 Synergy between Hoxa1 and Hoxb1: the relationship between arch patterning and the generation of cranial neural crest. Development (Cambridge, England) 90 11532923
2011 The JmjC domain-containing histone demethylase KDM3A is a positive regulator of the G1/S transition in cancer cells via transcriptional regulation of the HOXA1 gene. International journal of cancer 79 22020899
2008 The clinical spectrum of homozygous HOXA1 mutations. American journal of medical genetics. Part A 79 18412118
2018 Long non-coding RNA CCAT1 promotes multiple myeloma progression by acting as a molecular sponge of miR-181a-5p to modulate HOXA1 expression. Cell cycle (Georgetown, Tex.) 78 29228867
2011 Cardiovascular defects in a mouse model of HOXA1 syndrome. Human molecular genetics 76 21940751
1994 Characterization of Pax-6 and Hoxa-1 binding to the promoter region of the neural cell adhesion molecule L1. DNA and cell biology 76 7917011
2001 Generation of a novel functional neuronal circuit in Hoxa1 mutant mice. The Journal of neuroscience : the official journal of the Society for Neuroscience 71 11466434
1999 Compensatory defects associated with mutations in Hoxa1 restore normal palatogenesis to Hoxa2 mutants. Development (Cambridge, England) 68 10529419
2014 Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice. Science translational medicine 67 24382894
2016 HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner. Nucleic acids research 62 27382069
2004 Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism. Biological psychiatry 62 14960295
2007 Clinical characterization of the HOXA1 syndrome BSAS variant. Neurology 61 17875913
1996 Detection of HOXA1 expression in human breast cancer. Biochemical and biophysical research communications 59 8670198
2014 ACK1 tyrosine kinase interacts with histone demethylase KDM3A to regulate the mammary tumor oncogene HOXA1. The Journal of biological chemistry 58 25148682
1998 Hoxa1 and Krox-20 synergize to control the development of rhombomere 3. Development (Cambridge, England) 57 9806922
2018 miR-10a-5p Promotes Chondrocyte Apoptosis in Osteoarthritis by Targeting HOXA1. Molecular therapy. Nucleic acids 56 30731321
2007 HOXA1-stimulated oncogenicity is mediated by selective upregulation of components of the p44/42 MAP kinase pathway in human mammary carcinoma cells. Oncogene 56 17213808
2015 HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells. Oncology reports 54 26135141
2001 The recruitment of SOX/OCT complexes and the differential activity of HOXA1 and HOXB1 modulate the Hoxb1 auto-regulatory enhancer function. The Journal of biological chemistry 53 11278854
2015 MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells. Oncotarget 51 26417931
2010 Hoxa1 lineage tracing indicates a direct role for Hoxa1 in the development of the inner ear, the heart, and the third rhombomere. Developmental biology 51 20171203
2018 H3K27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the lncRNA HOTAIR. Annals of translational medicine 48 30596070
2011 Identification of novel Hoxa1 downstream targets regulating hindbrain, neural crest and inner ear development. Developmental biology 48 21784065
1998 Expression of Hoxa-1 and Hoxb-7 is regulated by extracellular matrix-dependent signals in mammary epithelial cells. Journal of cellular biochemistry 48 9620166
2015 Hoxb1 regulates proliferation and differentiation of second heart field progenitors in pharyngeal mesoderm and genetically interacts with Hoxa1 during cardiac outflow tract development. Developmental biology 46 26284287
2019 circEIF4G2 modulates the malignant features of cervical cancer via the miR‑218/HOXA1 pathway. Molecular medicine reports 45 30896864
2017 Dynamic regulation of Nanog and stem cell-signaling pathways by Hoxa1 during early neuro-ectodermal differentiation of ES cells. Proceedings of the National Academy of Sciences of the United States of America 45 28584089
2020 The LncRNA HOTAIRM1 Promotes Tamoxifen Resistance by Mediating HOXA1 Expression in ER+ Breast Cancer Cells. Journal of Cancer 43 32284737
2012 Protein interactions of the transcription factor Hoxa1. BMC developmental biology 42 23088713
2020 lncRNA CCAT1 Acts as a MicroRNA-218 Sponge to Increase Gefitinib Resistance in NSCLC by Targeting HOXA1. Molecular therapy. Nucleic acids 39 32084702
2020 lncRNA NEAT1 Binds to MiR-339-5p to Increase HOXA1 and Alleviate Ischemic Brain Damage in Neonatal Mice. Molecular therapy. Nucleic acids 39 32163893
2017 Hoxa1 targets signaling pathways during neural differentiation of ES cells and mouse embryogenesis. Developmental biology 38 28982536
2005 HOXA1 is required for E-cadherin-dependent anchorage-independent survival of human mammary carcinoma cells. The Journal of biological chemistry 38 16373333
2015 YAP regulates the expression of Hoxa1 and Hoxc13 in mouse and human oral and skin epithelial tissues. Molecular and cellular biology 36 25691658
2006 Induction of the homeotic gene Hoxa1 through valproic acid's teratogenic mechanism of action. Neurotoxicology and teratology 36 16989981
2019 LncRNA HOTAIRM1/HOXA1 Axis Promotes Cell Proliferation, Migration And Invasion In Endometrial Cancer. OncoTargets and therapy 35 31853186
2002 Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families. American journal of medical genetics 32 11840501
1995 Retinoic acid induces three newly cloned HOXA1 transcripts in MCF7 breast cancer cells. Biochemical and biophysical research communications 32 7488013
2020 lncRNA HotairM1 Depletion Promotes Self-Renewal of Cancer Stem Cells through HOXA1-Nanog Regulation Loop. Molecular therapy. Nucleic acids 31 33230449
2008 Hoxa1 is required for the retinoic acid-induced differentiation of embryonic stem cells into neurons. Journal of neuroscience research 31 18512762
2020 LncRNA HOTAIRM1 promotes MDSC expansion and suppressive functions through the HOXA1-miR124 axis during HCV infection. Scientific reports 30 33328510
2017 KDM3B shows tumor-suppressive activity and transcriptionally regulates HOXA1 through retinoic acid response elements in acute myeloid leukemia. Leukemia & lymphoma 30 28540746
2002 Targeted insertion results in a rhombomere 2-specific Hoxa2 knockdown and ectopic activation of Hoxa1 expression. Developmental dynamics : an official publication of the American Association of Anatomists 30 12412013
2002 Changing homeodomain residues 2 and 3 of Hoxa1 alters its activity in a cell-type and enhancer dependent manner. Nucleic acids research 28 12060683
1998 A conserved C-terminal domain in PBX increases DNA binding by the PBX homeodomain and is not a primary site of contact for the YPWM motif of HOXA1. The Journal of biological chemistry 28 9582372
2023 HOXA1 participates in VSMC-to-macrophage-like cell transformation via regulation of NF-κB p65 and KLF4: a potential mechanism of atherosclerosis pathogenesis. Molecular medicine (Cambridge, Mass.) 27 37528397
2020 microRNA-100 functions as a tumor suppressor in non-small cell lung cancer via regulating epithelial-mesenchymal transition and Wnt/β-catenin by targeting HOXA1. Thoracic cancer 27 32364673
2016 Hoxa1 and Hoxb1 are required for pharyngeal arch artery development. Mechanisms of development 26 27956219
2023 HOXA1 promotes aerobic glycolysis and cancer progression in cervical cancer. Cellular signalling 25 37286120
2020 Long Noncoding RNA ZFPM2-AS1 Knockdown Restrains the Development of Retinoblastoma by Modulating the MicroRNA-515/HOXA1/Wnt/β-Catenin Axis. Investigative ophthalmology & visual science 25 32561925
2021 Tumor-Suppressive Role of microRNA-202-3p in Hepatocellular Carcinoma Through the KDM3A/HOXA1/MEIS3 Pathway. Frontiers in cell and developmental biology 23 33520978
2020 Long non-coding RNA SNHG1 activates HOXA1 expression via sponging miR-193a-5p in breast cancer progression. Aging 23 32497022
2020 Long noncoding RNA HOTAIRM1 promotes myeloid-derived suppressor cell expansion and suppressive functions through up-regulating HOXA1 expression during latent HIV infection. AIDS (London, England) 21 33048872
2020 MiR-10a-5p restrains the aggressive phenotypes of ovarian cancer cells by inhibiting HOXA1. The Kaohsiung journal of medical sciences 21 33332731
2011 The Pbx interaction motif of Hoxa1 is essential for its oncogenic activity. PloS one 21 21957483
2017 MiR-99a suppresses cell invasion and metastasis in nasopharyngeal carcinoma through targeting HOXA1. OncoTargets and therapy 20 28228659
2012 The prolactin receptor mediates HOXA1-stimulated oncogenicity in mammary carcinoma cells. International journal of oncology 20 23064471
2007 HOXA1 gene variants influence head growth rates in humans. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 20 17171652
1998 An evolutionary conserved element is essential for somite and adjacent mesenchymal expression of the Hoxa1 gene. Developmental dynamics : an official publication of the American Association of Anatomists 20 9438427
2022 Elevated lncRNA-UCA1 upregulates EZH2 to promote inflammatory response in sepsis-induced pneumonia via inhibiting HOXA1. Carcinogenesis 19 35018436
2020 miR-100 Inhibits Cell Growth and Proliferation by Targeting HOXA1 in Nasopharyngeal Carcinoma. OncoTargets and therapy 19 32021301
2015 Understanding the molecular mechanisms of human microtia via a pig model of HOXA1 syndrome. Disease models & mechanisms 19 26035869
2013 Let-7c inhibits NSCLC cell proliferation by targeting HOXA1. Asian Pacific journal of cancer prevention : APJCP 19 23534758
2022 HOXA1, a breast cancer oncogene. Biochimica et biophysica acta. Reviews on cancer 18 35675857
2019 Long non-coding RNA 00152 promotes cell proliferation in cervical cancer via regulating miR-216b-5p/HOXA1 axis. European review for medical and pharmacological sciences 18 31114990
2019 Elevated microRNA-145 inhibits the development of oral squamous cell carcinoma through inactivating ERK/MAPK signaling pathway by down-regulating HOXA1. Bioscience reports 18 31138758
2018 Downregulation of microRNA-1469 promotes the development of breast cancer via targeting HOXA1 and activating PTEN/PI3K/AKT and Wnt/β-catenin pathways. Journal of cellular biochemistry 18 30320894
2000 Molecular cloning and analysis of a group of genes differentially expressed in cells which overexpress the Hoxa-1 homeobox gene. Experimental cell research 18 10942599
2019 A distal enhancer maintaining Hoxa1 expression orchestrates retinoic acid-induced early ESCs differentiation. Nucleic acids research 17 31147716
2012 Partial chromosome 7 duplication with a phenotype mimicking the HOXA1 spectrum disorder. Ophthalmic genetics 17 22950449
2005 Polyhistidine tract expansions in HOXA1 result in intranuclear aggregation and increased cell death. Biochemical and biophysical research communications 17 16168961
2004 No association between allelic variants of HOXA1/HOXB1 and autism. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 17 14681917
2019 MiR-99a suppressed cell proliferation and invasion by directly targeting HOXA1 through regulation of the AKT/mTOR signaling pathway and EMT in ovarian cancer. European review for medical and pharmacological sciences 16 31210292
2021 Silencing long non-coding RNA DLX6-AS1 or restoring microRNA-193b-3p enhances thyroid carcinoma cell autophagy and apoptosis via depressing HOXA1. Journal of cellular and molecular medicine 15 34514705
2020 miR-18a-3p Encourages Apoptosis of Chondrocyte in Osteoarthritis via HOXA1 Pathway. Current molecular pharmacology 15 32013856

Missed literature

Know a paper Affinage missed for HOXA1? Flag it for the maintainers and the community.

No submissions yet.