Affinage

HOXA1

Homeobox protein Hox-A1 · UniProt P49639

Length
335 aa
Mass
36.7 kDa
Annotated
2026-04-28
100 papers in source corpus 38 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

HOXA1 is a homeodomain transcription factor that serves as a master regulator of early hindbrain patterning, neural crest specification, and cardiac outflow tract development, acting as a primary transducer of retinoic acid signaling during embryogenesis. HOXA1 cooperates with PBX cofactors through its YPWM motif to bind composite Hox-Pbx DNA sites, directly activating targets including EphA2 and the Hoxb1 autoregulatory enhancer, and synergizes with HOXB1 to specify rhombomere 4/5 identity and generate cranial neural crest cells (PMID:1680563, PMID:9733765, PMID:9463359, PMID:11532923). Its transcription is induced by retinoic acid through a 3′ RARE-containing enhancer and is epigenetically modulated by Polycomb (SUZ12/EZH2-mediated H3K27me3), H3K9 demethylases KDM3A and KDM3B, and lncRNAs linc-HOXA1 and HOTAIRM1 that regulate chromatin modifier access at the HOXA1 locus (PMID:1360810, PMID:17663992, PMID:23723417, PMID:25148682, PMID:30376874). Beyond its canonical transcriptional roles, HOXA1 activates NF-κB signaling through a non-transcriptional mechanism involving physical interaction with RBCK1/HOIL-1 and TRAF2, and promotes oncogenic transformation of mammary epithelial cells by upregulating Bcl-2 and the p44/42 MAPK pathway (PMID:27382069, PMID:12482855, PMID:17213808).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1991 High

    Establishing that Hoxa1 is essential for hindbrain segmentation resolved the question of whether individual Hox genes have non-redundant roles in anteroposterior patterning, revealing that Hoxa1 loss causes rhombomere 4–7 defects, cranial nerve agenesis, and inner ear malformations.

    Evidence Homologous recombination gene targeting producing Hoxa1 null mice in two independent labs

    PMID:1346922 PMID:1680563

    Open questions at the time
    • Direct transcriptional targets of Hoxa1 in the hindbrain were unknown
    • Whether Hoxa1 acts cell-autonomously was not established
    • Cofactor requirements for Hoxa1 DNA binding were undefined
  2. 1992 High

    Identifying a 3′ retinoic acid response element–containing enhancer established how RA directly activates Hoxa1 transcription, placing Hoxa1 as a primary RA-responsive gene in the Hox cascade.

    Evidence DNase I hypersensitivity mapping, lacZ reporter transgenic mice, RARE point mutations in F9 cells and in vivo

    PMID:1360810 PMID:7743939

    Open questions at the time
    • The identity of trans-acting factors beyond RAR/RXR at the enhancer was unknown
    • Epigenetic regulation of the RARE locus had not been explored
  3. 1998 High

    Demonstrating that the YPWM motif mediates cooperative DNA binding with PBX cofactors, and that HOXA1/PBX1/HOXB1 activate EphA2 and the Hoxb1 autoregulatory enhancer, defined the molecular logic by which Hoxa1 engages its transcriptional targets in hindbrain patterning.

    Evidence EMSA with YPWM mutagenesis, co-transfection reporter assays, transgenic embryo analysis, Hoxa1/Hoxb1 double-mutant mice

    PMID:11278854 PMID:9582372 PMID:9733765

    Open questions at the time
    • Genome-wide binding sites for HOXA1 were unknown
    • Whether homeodomain residue differences between paralogs affect target selection in vivo was untested
  4. 1998 High

    Compound Hoxa1/Hoxb1 double-mutant analyses revealed overlapping paralog functions in rhombomere 4/5 identity, second arch formation, and ear development that are cryptic in single mutants, establishing the genetic redundancy framework for Hox1 paralogs.

    Evidence Double knockout mice with neurofilament staining, retrograde labeling, molecular marker analysis

    PMID:10529420 PMID:10662633 PMID:9463349 PMID:9463359

    Open questions at the time
    • Whether functional redundancy reflects protein equivalence or regulatory overlap was unresolved
    • Cell-autonomous versus non-cell-autonomous contributions were not distinguished
  5. 2001 High

    Cell-autonomous requirement for Hoxa1/Hoxb1 in neural crest generation from r4 was established through grafting experiments, showing that Hoxa1 acts within neuroepithelium to specify neural crest competence rather than through secondary signaling.

    Evidence Ectoderm-specific double-mutant mice, grafting experiments in cultured embryos, lineage analysis

    PMID:11532923

    Open questions at the time
    • Direct neural crest gene targets of Hoxa1 were not identified
    • How Hoxa1 interfaces with neural crest induction pathways (Foxd3, Sox9) was mechanistically unclear
  6. 2002 High

    Protein-swap knock-in experiments showed that HOXA1 and HOXB1 coding sequences are functionally interchangeable, demonstrating that paralog subfunctionalization is driven by regulatory element divergence rather than protein sequence differences.

    Evidence Knock-in mice with swapped coding regions, insertion of Hoxb1 autoregulatory enhancer into Hoxa1 locus

    PMID:16890163

    Open questions at the time
    • Whether this interchangeability extends beyond hindbrain patterning to other tissues was not tested
    • Post-translational modifications distinguishing paralogs were not addressed
  7. 2002 Medium

    Discovery that forced HOXA1 expression transforms mammary epithelial cells via Bcl-2 upregulation and survival signaling expanded HOXA1 function beyond developmental patterning into oncogenic contexts.

    Evidence Forced expression in mammary cells, soft agar assays, tumor formation, Bcl-2 reporter assays

    PMID:12482855

    Open questions at the time
    • Whether Bcl-2 is a direct transcriptional target (Hoxa1 binding at Bcl-2 regulatory regions) was not confirmed by ChIP
    • Relevance to endogenous breast cancer was correlative
  8. 2007 Medium

    Placing HOXA1 upstream of the p44/42 MAPK pathway through transcriptional activation of GRB2 and MEK1 defined the signaling axis through which HOXA1 promotes proliferation and transformation, with MEK inhibition blocking HOXA1 oncogenic activity.

    Evidence Microarray profiling, HOXA1 forced expression/depletion, MEK1 inhibitor epistasis, Western blot

    PMID:17213808

    Open questions at the time
    • Direct binding of HOXA1 to GRB2/MEK1 regulatory regions was not shown
    • In vivo relevance of the MAPK axis in HOXA1-driven tumors was not tested
  9. 2007 Medium

    Revealing that SUZ12/PRC2 occupies the Hoxa1 RARE before RA treatment and is displaced upon RA exposure established the Polycomb-to-activation chromatin switch governing Hoxa1 induction, linking epigenetic silencing to the RA signaling response.

    Evidence ChIP for SUZ12, H3K27me3, H3ac, H3K4me2, and RNA Pol II in F9 embryonal carcinoma cells ± RA

    PMID:17663992

    Open questions at the time
    • The mechanism of PRC2 displacement was unknown
    • Whether additional chromatin remodelers participate was not tested
  10. 2010 High

    Lineage tracing with Hoxa1-IRES-Cre revealed that Hoxa1-expressing cells contribute directly to the otic epithelium, cardiac atria, outflow tract, and rhombomere 3, expanding the known developmental domains of Hoxa1 beyond the hindbrain.

    Evidence Cre-mediated lineage tracing in mouse embryos

    PMID:20171203

    Open questions at the time
    • Functional requirement for Hoxa1 in cardiac and otic lineages was not established in this study
    • Whether contributions to r3 reflect early transient expression was unclear
  11. 2011 High

    Characterization of cardiovascular defects in Hoxa1 nulls (interrupted aortic arch, Tetralogy of Fallot) and identification of downstream targets (Zic1, Foxd3, Hnf1b, Pax8) by microarray placed Hoxa1 as a regulator of cardiac neural crest specification and defined its developmental gene network.

    Evidence Hoxa1 null cardiac phenotyping, microarray on microdissected embryonic tissue, compound mutant analysis with Hoxb1

    PMID:21784065 PMID:21940751 PMID:26284287

    Open questions at the time
    • Direct binding of Hoxa1 to these downstream target promoters/enhancers was not shown
    • Functional rescue experiments for individual targets were not performed
  12. 2013 High

    Discovery that lncRNA linc-HOXA1 represses Hoxa1 in cis by recruiting PURB established a novel regulatory layer operating at the single-chromosome level, with RA overriding this repression during differentiation.

    Evidence Single-cell transcript counting, RNA FISH, allele-specific siRNA knockdown, PURB identification

    PMID:23723417

    Open questions at the time
    • The mechanism by which PURB mediates transcriptional repression was undefined
    • Whether linc-HOXA1 regulation operates in vivo during embryogenesis was not shown
  13. 2014 High

    Identification of ACK1-mediated phosphorylation of KDM3A (Y1114) as an activating signal for H3K9 demethylation at the HOXA1 promoter linked receptor tyrosine kinase signaling to HOXA1 epigenetic de-repression, connecting growth factor signaling with HOXA1 transcriptional control.

    Evidence In vitro kinase assay, phospho-site mutagenesis, ChIP for H3K9me2, pharmacological inhibitors

    PMID:25148682

    Open questions at the time
    • Whether this ACK1-KDM3A-HOXA1 axis operates during normal development was not tested
    • Additional substrates of ACK1 at the HOXA1 locus were not explored
  14. 2016 High

    Demonstrating that HOXA1 activates NF-κB signaling non-transcriptionally through physical interaction with RBCK1/HOIL-1 and TRAF2 via its His-repeat and homeodomain revealed an unexpected cytoplasmic signaling function for a homeodomain transcription factor, required for its oncogenic activity.

    Evidence Yeast two-hybrid, co-immunoprecipitation, NF-κB reporter assays, domain deletion/mutagenesis, epistasis experiments

    PMID:27382069

    Open questions at the time
    • Whether HOXA1-RBCK1/TRAF2 complexes form in physiological developmental contexts was untested
    • The stoichiometry and dynamics of HOXA1 partitioning between nuclear and cytoplasmic functions were unknown
  15. 2017 High

    Genome-wide ChIP-seq in differentiating ES cells mapped Hoxa1 occupancy to enhancers co-bound by Nanog and Hox cofactors, establishing direct cross-regulatory repression between Hoxa1 and the pluripotency network and defining HOXA1's genome-wide target repertoire across Wnt, TGF-β, Hedgehog, and Hippo pathway genes.

    Evidence ChIP-seq in RA-treated ES cells, reciprocal binding analysis, cross-species validation in mouse and zebrafish transgenic reporters

    PMID:28584089 PMID:28982536

    Open questions at the time
    • Functional validation of individual enhancer targets beyond Dok5 and Wls1 was limited
    • Time-resolved binding dynamics during the RA response were not captured
  16. 2018 Medium

    Studies in cancer cells showed that lncRNA HOTAIRM1 modulates HOXA1 expression bidirectionally — activating it in glioblastoma by sequestering G9a, EZH2, and DNMTs away from the TSS, and in other contexts recruiting EZH2/SUZ12 to silence it — revealing context-dependent epigenetic regulation of HOXA1 by the same lncRNA.

    Evidence RNA-ChIP, ChIP for H3K9me2/H3K27me3, bisulfite sequencing, RIP for HOTAIRM1-EZH2, HOTAIRM1 knockdown

    PMID:30376874 PMID:32284737 PMID:33230449

    Open questions at the time
    • Contradictory roles of HOTAIRM1 (activating vs. silencing HOXA1) in different cell types were not reconciled mechanistically
    • In vivo developmental relevance of HOTAIRM1-HOXA1 regulation was not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The structural basis for HOXA1's dual nuclear (transcription factor) and cytoplasmic (NF-κB activation) functions, and how cells partition HOXA1 between these roles during development versus oncogenesis, remains unresolved.
  • No crystal or cryo-EM structure of HOXA1 alone or in complex with PBX/RBCK1
  • Mechanism by which HOXA1 partitions between transcriptional and non-transcriptional functions is unknown
  • Whether HOXA1's NF-κB activation has any developmental role has not been tested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 7 GO:0003677 DNA binding 6 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 6 GO:0005829 cytosol 2
Pathway
R-HSA-1266738 Developmental Biology 8 R-HSA-74160 Gene expression (Transcription) 8 R-HSA-4839726 Chromatin organization 7 R-HSA-162582 Signal Transduction 3
Partners
EZH2HOXB1KDM3APBX1PURBRBCK1SUZ12TRAF2

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 Targeted disruption of Hox-1.6 (Hoxa1) in mice causes defects in rhombomeres 4-7, including absence of cranial nerves and ganglia, and malformed inner ears and skull bones, demonstrating Hoxa1 is required for regional specification along the rostrocaudal axis in its most rostral domain of expression. Homologous recombination gene targeting in embryonic stem cells, mouse knockout Cell High 1346922 1680563
1992 A retinoic acid-responsive enhancer located 3' of the Hoxa1 gene (containing a RARE identical to that of RARbeta) is required for retinoic acid-induced transcriptional activation of Hoxa1; the RARE alone is insufficient and other sequences within the enhancer also contribute. DNase I hypersensitivity mapping, lacZ minigene reporter assays in transgenic mice, F9 teratocarcinoma cell transfection Mechanisms of development High 1360810
1995 An evolutionarily conserved enhancer within the Hoxa1 locus containing a retinoic acid response element drives expression in neuroepithelium caudal to rhombomere 4; point mutations in the RARE abolish this expression, supporting a direct role for endogenous retinoids in Hoxa1 regulation and hindbrain patterning. Transgenic mouse reporter assays with RARE point mutations Development (Cambridge, England) High 7743939
1998 HOXA1 and HOXB1, together with cofactor PBX1, bind to Hox-Pbx consensus sites in the EphA2 enhancer and transcriptionally activate EphA2 expression; this is required for rhombomere 4-specific EphA2 expression in vivo, as EphA2 expression is reduced in Hoxa1/Hoxb1 double mutants. In vitro DNA binding (EMSA/co-immunoprecipitation), co-transfection reporter assays, transgenic embryo analysis, double-mutant mice The Journal of biological chemistry High 9733765
1998 Hoxa1 and Hoxb1 genetically synergize to pattern the hindbrain, cranial nerves, and second pharyngeal arch; double null mutants show loss of all second arch-derived elements and complete disruption of ear development, phenotypes not seen in single mutants. Genetic epistasis via compound double-mutant mice, neurofilament staining, retrograde motor neuron labeling Development (Cambridge, England) High 9463349 9463359
1998 Hoxa1 is the primary mediator of the retinoic acid response of the Hoxb1 autoregulatory enhancer (b1-ARE) in vivo; this function requires binding of SOX/OCT heterodimers to the b1-ARE. HOXA1 has significantly lower transcriptional activity than HOXB1 from the b1-ARE, with the differential activity mapped to the HOXB1 N-terminal transcriptional activation domain. Transgenic mice, cell transfection reporter assays, SOX/OCT site mutagenesis, analysis of Hoxa1 mutant mice The Journal of biological chemistry High 11278854
1998 Hoxa1 is required to set the anterior limit of Hoxb1 expression at the r3/r4 boundary; loss of Hoxa1 initiates a cascade of gene misexpressions causing misspecification of hindbrain compartments r2 through r5, followed by ectopic apoptosis. Genetic epistasis via single and double knockout mice, molecular marker analysis Development (Cambridge, England) High 10662633
1998 The YPWM motif of HOXA1 is strictly required for cooperative DNA binding with PBX cofactors in vitro and in vivo; the YPWM motif contacts the PBX homeodomain. The GKFQ domain of PBX increases DNA binding by PBX but is not a primary contact site for HOXA1's YPWM motif. In vitro DNA binding assays (EMSA), co-transfection, deletion/mutagenesis of E2A-PBX The Journal of biological chemistry High 9582372
1999 Hoxa1 and Hoxb1 double mutants show loss of both rhombomeres 4 and 5 and selective loss of the second branchial arch, demonstrating overlapping functions in rhombomere identity specification; the aberrant hindbrain subsequently undergoes size regulation through apoptosis. Double knockout mice, molecular marker analysis, histology Development (Cambridge, England) High 10529420
2001 Hoxa1 synergizes with Hoxb1 to generate cranial neural crest cells from r4; loss of both genes in the neuroepithelium reduces r4 size and abolishes its ability to generate neural crest cells in a cell-autonomous manner. Ectoderm-specific double-mutant mice, molecular and lineage analysis, grafting experiments in cultured embryos Development (Cambridge, England) High 11532923
2001 Ectopic neuronal groups established by misspecification in Hoxa1 null mice (from the r3-r4 level, including r2-identity progenitors) form a supernumerary functional neuronal circuit that integrates the respiratory rhythm-generating network at birth. Hoxa1 null mouse analysis, electrophysiology, neuroanatomical tracing The Journal of neuroscience Medium 11466434
2002 HOXA1 is functionally interchangeable with HOXB1 when protein-coding sequences are swapped at the respective loci in mice, demonstrating that subfunctionalization of Hox1 paralogs is mediated primarily by divergence of transcriptional regulatory elements rather than protein sequence differences. Knock-in mouse lines with swapped coding regions, insertion of Hoxb1 autoregulatory enhancer into Hoxa1 locus Developmental cell High 16890163
2002 Hoxa1 homeodomain residues 2 and 3 (asparagine and alanine, unusual compared to typical basic residues) function as specificity determinants when Hoxa1 acts as a monomer, but do not influence target specificity in Pbx1a-Hoxa1 heterodimers in vitro; however, on the Hoxb1 autoregulatory enhancer these residues can modulate Hoxa1 activity even in the presence of Pbx, in a cell-type-dependent manner. Site-directed mutagenesis, cell transfection reporter assays, in vitro DNA binding Nucleic acids research Medium 12060683
2002 Forced HOXA1 expression in human mammary carcinoma cells upregulates Bcl-2 transcription, promotes cell survival, anchorage-independent growth, and oncogenic transformation of immortalized mammary epithelial cells with in vivo tumor formation. Forced expression in human mammary cells, soft agar colony formation, in vivo tumor formation, Bcl-2 reporter assays The Journal of biological chemistry Medium 12482855
2005 E-cadherin-mediated cell-cell contact increases HOXA1 expression in mammary carcinoma cells through Rac1 signaling; HOXA1 is required downstream of E-cadherin for anchorage-independent proliferation and survival. E-cadherin blocking antibody, EGTA treatment, calcium rescue, Rac1 inhibition, HOXA1 siRNA knockdown The Journal of biological chemistry Medium 16373333
2007 HOXA1-mediated oncogenic transformation of mammary epithelial cells requires activation of the p44/42 MAP kinase pathway; HOXA1 transcriptionally upregulates GRB2 and MEK1 and increases ERK phosphorylation, and MEK1 inhibition blocks HOXA1-driven proliferation, survival, and transformation. Microarray gene expression profiling, forced expression/depletion of HOXA1, MEK1 inhibitor treatment, Western blot Oncogene Medium 17213808
2007 Polycomb group protein SUZ12 associates with the Hoxa1 RARE prior to retinoic acid treatment; RA treatment attenuates SUZ12 association and decreases H3K27me3 at the Hoxa1 RARE, while increasing H3ac, H3K4me2, and RNA Pol II occupancy. RAR-gamma and RXR-alpha are present at the RARE before and during RA treatment. Chromatin immunoprecipitation (ChIP) in F9 embryonal carcinoma cells Journal of molecular biology Medium 17663992
2008 Hoxa1 is required for retinoic acid-induced neuronal differentiation of embryonic stem cells; Hoxa1 null ES cells fail to express neuronal markers and instead upregulate endodermal markers (Sox17); re-introduction of Hoxa1 rescues neuronal differentiation. Hoxa1 may promote neural differentiation by inhibiting Sox17 expression. Hoxa1 null ES cells, RA-induced differentiation protocol, marker expression analysis, Hoxa1 rescue by metallothionein-driven re-expression Journal of neuroscience research Medium 18512762
2010 Hoxa1 lineage tracing using Hoxa1-IRES-Cre mice reveals that Hoxa1-expressing precursors contribute directly to the otic epithelium (except sensory patches), atria and outflow tract of the developing heart, and rhombomere 3—demonstrating broader direct roles for Hoxa1 than previously recognized. Cre-mediated lineage tracing (Hoxa1-IRES-Cre), reporter gene activation in mouse embryos Developmental biology High 20171203
2011 Hoxa1 null mice display cardiovascular defects including interrupted aortic arch, aberrant subclavian artery, and Tetralogy of Fallot; Hoxa1 is expressed in precursors of cardiac neural crest cells and acts upstream of genes controlling neural crest specification, indicating Hoxa1 regulates heart development via cardiac NCCs. Hoxa1 null mice, cardiac morphology analysis, gene expression analysis of NCC specification markers Human molecular genetics High 21940751
2011 Histone demethylase KDM3A (JMJD1A) activates HOXA1 transcription by demethylating H3K9me2 at the HOXA1 promoter; KDM3A knockdown reduces HOXA1 and CCND1 levels causing G1 arrest, and KDM3A expression positively correlates with HOXA1 in cancer cell lines. siRNA knockdown of KDM3A, ChIP showing KDM3A binding to HOXA1 promoter, H3K9me2 demethylation assay, cell cycle analysis International journal of cancer Medium 22020899
2011 Microarray analysis of Hoxa1 null embryos identified downstream targets of Hoxa1 including Zic1, Hnf1b, Foxd3 (neural crest induction), Pax8 and Fgfr3 (inner ear), and Lhx5 (brainstem neurons), placing Hoxa1 upstream of these genes in a developmental genetic cascade. Microarray on microdissected Hoxa1 null vs. wild-type embryo tissue, gene expression validation Developmental biology Medium 21784065
2012 Hoxa1 interacts with a broad network of proteins including components of cell-signaling transduction, cell adhesion, and vesicular trafficking, as identified by a systematic yeast two-hybrid screen against ~12,200 ORFs; 45 interactions confirmed by affinity co-purification, and 41 by Bimolecular Fluorescence Complementation revealing distinct intracellular localization patterns (vesicular, cytoplasmic, and nuclear compartments). Yeast two-hybrid screen, affinity co-purification in animal cell lines, Bimolecular Fluorescence Complementation BMC developmental biology Medium 23088713
2013 The lncRNA linc-HOXA1, located ~50 kb from the Hoxa gene cluster, represses Hoxa1 transcription in cis by recruiting the protein PURB as a transcriptional cofactor; single-cell transcript counting shows anti-correlated expression of linc-HOXA1 and Hoxa1, and knockdown of linc-HOXA1 at its transcription site increases Hoxa1 transcription on the same chromosome. Retinoic acid disrupts this repression. Single-cell transcript counting, RNA FISH, siRNA knockdown, cis-acting analysis by allele-specific manipulation Genes & development High 23723417
2014 ACK1 tyrosine kinase phosphorylates the histone demethylase KDM3A at tyrosine 1114 in a heregulin-dependent manner, decreasing H3K9me2 deposition and thereby increasing HOXA1 transcription; inhibition of ACK1 restores H3K9me2 marks and suppresses HOXA1 expression, conferring tamoxifen resistance. In vitro kinase assay, phospho-site mutagenesis, ChIP for H3K9me2, small-molecule ACK1 inhibitors (AIM-100, Dasatinib), siRNA knockdown The Journal of biological chemistry High 25148682
2015 YAP (Hippo pathway transcriptional coactivator) regulates Hoxa1 expression in oral and dental epithelial tissues; ChIP assay implicates TEAD transcription factors as mediators of YAP-driven Hoxa1 regulation, and sphere formation assays show Hoxa1 is functionally involved in YAP-regulated epithelial progenitor proliferation. RNA-Seq, in situ hybridization, ChIP (YAP/TEAD), sphere formation assay, Yap conditional knockout and transgenic mice Molecular and cellular biology Medium 25691658
2015 Hoxa1 and Hoxb1 are expressed in a sub-population of second heart field progenitors contributing to the cardiac outflow tract; compound Hoxa1−/−; Hoxb1+/− embryos display outflow tract defects with premature SHF differentiation, demonstrating redundant roles for Hoxa1 and Hoxb1 in outflow tract development upstream of FGF/ERK and BMP/SMAD signaling. Compound mutant mice, SHF marker analysis, FGF/ERK and BMP/SMAD pathway analysis Developmental biology Medium 26284287
2016 HOXA1 physically interacts with RBCK1/HOIL-1 and TRAF2 (TNFR-associated proteins) via its 11-His repeat and homeodomain, and activates NF-κB signaling upstream of IκB through a non-transcriptional mechanism; RBCK1 and TRAF2 influences on NF-κB are epistatic to HOXA1. NF-κB activation is required for HOXA1 oncogenic activity. Proteome-wide yeast two-hybrid, co-immunoprecipitation, reporter assays for NF-κB, domain deletion/mutagenesis, epistasis experiments Nucleic acids research High 27382069
2017 Genome-wide Hoxa1 binding analysis in differentiating ES cells reveals that Hoxa1 is rapidly recruited to target sites co-occupied by Nanog; Hoxa1 binds regulatory regions of Nanog, and Nanog binds the 3' enhancer of Hoxa1, establishing direct cross-regulatory mutual repression between Hoxa1 and the core pluripotency network. Hoxa1 also binds regulatory regions of Sox2, Esrrb, and Myc. ChIP-seq, genome-wide occupancy mapping, expression analysis, retinoic acid-induced ES cell differentiation Proceedings of the National Academy of Sciences of the United States of America High 28584089
2017 Genome-wide Hoxa1 binding in differentiating ES cells maps to enhancer regions co-occupied by Hox cofactors; Hoxa1 targets multiple components of major signaling pathways (Wnt, TGF-β, Hedgehog, Hippo) and genes involved in neural crest migration, inner ear development, and heart development; two enhancers in Dok5 and Wls1 were validated for neural expression in mouse and zebrafish. ChIP-seq, differential gene expression analysis in Hoxa1 gain- and loss-of-function mouse and zebrafish, transgenic reporter assays Developmental biology High 28982536
2017 KDM3B binds retinoic acid response elements (but not the promoter) of HOXA1 and demethylates H3K9 at those sites to transcriptionally activate HOXA1; KDM3B knockdown increases H3K9me1 but decreases H3K9me2 at the RARE region of HOXA1. KDM3B overexpression and knockdown, ChIP for KDM3B binding and H3K9 methylation marks, microarray profiling Leukemia & lymphoma Medium 28540746
2018 The lncRNA HOTAIRM1 activates HOXA1 transcription in GBM by sequestering histone methyltransferases G9a (H3K9me2) and EZH2 (H3K27me3) and DNA methyltransferases (DNMT1, DNMT3b) away from the HOXA1 gene TSS, causing histone and DNA demethylation at that locus. ChIP assay for histone marks, RNA-ChIP for HOTAIRM1-protein interactions, bisulfite sequencing PCR for DNA methylation, HOTAIRM1 knockdown Journal of experimental & clinical cancer research Medium 30376874
2020 The lncRNA HOTAIRM1 prevents PRC2 complex (EZH2) from binding the HOXA1 promoter and depositing H3K27me3, thereby maintaining HOXA1 expression in tamoxifen-resistant breast cancer cells; HOTAIRM1 directly interacts with EZH2. RNA immunoprecipitation (RIP) for HOTAIRM1-EZH2 interaction, ChIP for H3K27me3 at HOXA1 promoter, HOTAIRM1 knockdown Journal of Cancer Medium 32284737
2020 LncRNA HotairM1 recruits EZH2 and SUZ12 to the HOXA1 promoter, inducing H3K27 trimethylation and epigenetic silencing of HOXA1; silencing of HOXA1 subsequently induces H3K27 acetylation at the Nanog enhancer, upregulating Nanog expression and promoting cancer stem cell self-renewal in a reciprocal HOXA1-Nanog loop. ChIP for H3K27me3 and H3K27ac, EZH2/SUZ12 recruitment assay, HOXA1 knockdown, Nanog expression analysis Molecular therapy. Nucleic acids Medium 33230449
1994 Hoxa1 homeodomain protein binds to a site approximately 60 bp upstream of the L1 neural cell adhesion molecule transcription start site, as demonstrated by in vitro DNA binding assays; this site is also recognized by Pax-6. In vitro DNA binding (gel shift/footprinting) DNA and cell biology Low 7917011
2023 HOXA1 transcriptionally activates NF-κB RelA (p65) and KLF4 in vascular smooth muscle cells, promoting VSMC-to-macrophage-like phenotypic transformation; HOXA1 knockdown in ApoE−/− mice reduces atherosclerotic plaque formation and VSMC transdifferentiation. AAV1-shHOXA1 knockdown in ApoE−/− mice, in vitro VSMC model, Western blot, ChIP (implied by transcriptional activation claim) Molecular medicine (Cambridge, Mass.) Low 37528397

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1991 Regionally restricted developmental defects resulting from targeted disruption of the mouse homeobox gene hox-1.5. Nature 755 1673020
1991 Disruption of the Hox-1.6 homeobox gene results in defects in a region corresponding to its rostral domain of expression. Cell 637 1680563
1992 Developmental defects of the ear, cranial nerves and hindbrain resulting from targeted disruption of the mouse homeobox gene Hox-1.6. Nature 481 1346922
1990 Variations of cervical vertebrae after expression of a Hox-1.1 transgene in mice. Cell 347 1970515
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
1992 Identification of a retinoic acid responsive enhancer 3' of the murine homeobox gene Hox-1.6. Mechanisms of development 245 1360810
1989 Craniofacial abnormalities induced by ectopic expression of the homeobox gene Hox-1.1 in transgenic mice. Cell 240 2568891
2005 Homozygous HOXA1 mutations disrupt human brainstem, inner ear, cardiovascular and cognitive development. Nature genetics 214 16155570
1990 The segment-specific gene Krox-20 encodes a transcription factor with binding sites in the promoter region of the Hox-1.4 gene. The EMBO journal 190 1969796
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
1989 Transgenic mice overexpressing the mouse homoeobox-containing gene Hox-1.4 exhibit abnormal gut development. Nature 185 2563568
1989 Mouse homeo-genes within a subfamily, Hox-1.4, -2.6 and -5.1, display similar anteroposterior domains of expression in the embryo, but show stage- and tissue-dependent differences in their regulation. Development (Cambridge, England) 184 2576400
1993 Specification of axial identity in the mouse: role of the Hoxa-5 (Hox1.3) gene. Genes & development 167 7901120
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
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
1988 Mouse homeobox gene transcripts occupy different but overlapping domains in embryonic germ layers and organs: a comparison of Hox-3.1 and Hox-1.5. Development (Cambridge, England) 134 2904354
1993 The establishment of murine Hox-1 expression domains during patterning of the limb. Developmental biology 131 8099045
1989 The Hox-1.3 homeo box protein is a sequence-specific DNA-binding phosphoprotein. Genes & development 130 2565857
2002 Human growth hormone-regulated HOXA1 is a human mammary epithelial oncogene. The Journal of biological chemistry 127 12482855
1987 Hox-1.6: a mouse homeo-box-containing gene member of the Hox-1 complex. The EMBO journal 118 2891503
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