Affinage

HOXB1

Homeobox protein Hox-B1 · UniProt P14653

Length
301 aa
Mass
32.2 kDa
Annotated
2026-06-10
76 papers in source corpus 34 papers cited in narrative 34 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

HOXB1 is a homeodomain transcription factor that establishes and maintains the segmental identity of rhombomere 4 (r4) in the developing hindbrain, acting as a segment-determining selector gene whose ectopic expression homeotically transforms other rhombomeres toward r4 fate (PMID:10381880). It binds DNA cooperatively with PBX1/EXD cofactors through its hexapeptide motif, which inserts into a hydrophobic pocket of PBX1; a 2.35 Å crystal structure of the HOXB1-PBX1-DNA ternary complex defined this interaction, showing PBX1 contributes an additional helix that stabilizes hexapeptide binding and DNA contacts (PMID:10052460). Through such Hox/Pbx (and Prep1/Meis-containing) motifs, HOXB1 autoregulates its own r4 enhancer and directly cross-regulates the segmental targets Hoxb2, Hoxa2, and the EphA2 receptor (PMID:7600572, PMID:9242495, PMID:17113575, PMID:9733765). Beyond classical activation, genome-wide binding shows HOXB1 co-occupies a large repressive set of sites with REST and represses transcription through a defined HB1RE motif, indicating it functions in both activating and repressive modes (PMID:33546292). HOXB1 expression is induced by retinoic acid via distinct DR2 and DR5 RAREs in its promoter and 3' enhancers and is spatially restricted by a repressive RARE and by direct binding of the repressor Hoxb3 (PMID:7914354, PMID:9671595, PMID:21320481). Functionally, HOXB1 specifies facial branchiomotor neuron identity and migration—operating through a Hoxb1→GATA2→GATA3 cascade—such that its loss re-specifies r4-derived neurons toward an r2-like (trigeminal) fate, abolishes the VIIth nerve somatic motor component, and triggers apoptotic clearance of mispatterned neurons (PMID:8898234, PMID:8967950, PMID:10556076, PMID:14522873). It is additionally required in r4-derived neural crest for VIIth nerve maintenance, in olivocochlear efferent motor neurons whose defective innervation causes sensorineural hearing loss, in vestibulospinal tract neuron formation, and in pharyngeal mesoderm for outflow tract development (PMID:15198977, PMID:37738262, PMID:26730404, PMID:26284287). A homozygous human HOXB1 founder missense mutation (Arg207Cys) that destabilizes the HOXB1:PBX1:DNA complex causes a bilateral facial palsy syndrome recapitulating the mouse knockout (PMID:22770981).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Established that retinoic acid signaling directly controls Hoxb1 spatial expression, answering how an early morphogen sets and sharpens segment-restricted Hox boundaries.

    Evidence RARE point mutations in transgenic mouse reporters, validated across mouse, chick, and Fugu

    PMID:7914354 PMID:7916164

    Open questions at the time
    • Identity of the RAR/RXR receptors and coactivators acting in vivo not resolved
    • Does not explain how RA gradients are converted into a sharp r4 boundary
  2. 1995 High

    Defined HOXB1 as an autoregulatory factor requiring PBX/EXD cofactors at its r4 enhancer, answering how Hox identity is locked in once initiated.

    Evidence In vitro DNA binding plus transgenic mouse and Drosophila reporter assays

    PMID:7600572

    Open questions at the time
    • Did not establish the structural basis of cooperativity
    • Full set of enhancer cofactors incompletely defined
  3. 1995 Medium

    Mapped the RA-responsive promoter architecture to DR-2 RAR/RXR sites coupled to tissue-specific coactivators, refining how RA input is converted into context-specific HOXB1 activation.

    Evidence Reporter assays and receptor/coactivator binding mapping of 5' and 3' RA-responsive elements

    PMID:7831296 PMID:7831297

    Open questions at the time
    • Molecular identity of the proposed retinoid-inducible coactivators not determined
    • In vivo relevance not tested by mutagenesis
  4. 1996 High

    Knockouts showed Hoxb1 is required for facial branchiomotor neuron specification and migration, converting the molecular autoregulation story into an organismal function.

    Evidence Two independent targeted mouse alleles with histology, DiI lineage tracing, and molecular markers

    PMID:8898234 PMID:8967950

    Open questions at the time
    • Direct transcriptional targets driving migration not identified at this stage
    • Cell-autonomous versus non-autonomous requirements unresolved
  5. 1997 High

    Identified Hoxb2 as a direct downstream target via a bipartite Hox/Pbx enhancer, establishing HOXB1 as the apex of a hindbrain Hox cross-regulatory network.

    Evidence Transgenic deletion analysis, in vitro binding, and Hoxb1 knockout showing loss of r4 Hoxb2 induction

    PMID:9242495

    Open questions at the time
    • Functional consequence of Hoxb2 loss in r4 not addressed here
  6. 1998 High

    Extended the direct target repertoire to EphA2 and the foregut DR5 RARE, showing HOXB1 controls both receptor signaling components and gut-versus-hindbrain enhancer usage.

    Evidence EMSA, reporter transactivation, transgenic and double-mutant analysis (EphA2); transgenic DR5 RARE mutagenesis (foregut)

    PMID:9671595 PMID:9733765

    Open questions at the time
    • Functional role of HOXB1 in foregut organs not phenotypically defined
    • Redundancy with HOXA1 at EphA2 not fully dissected
  7. 1999 High

    Solved the HOXB1-PBX1-DNA crystal structure, answering at atomic resolution how the hexapeptide drives cooperative heterodimer DNA binding.

    Evidence 2.35 Å X-ray crystallography of the ternary complex

    PMID:10052460

    Open questions at the time
    • Structure of higher-order Prep1/Meis-containing complexes not solved
    • Does not address activation versus repression switching
  8. 1999 High

    Demonstrated by gain-of-function that Hoxb1 is sufficient to confer r4 identity, and placed Hoxb1 atop a GATA2→GATA3 cascade for branchiomotor neuron specification.

    Evidence Retroviral misexpression/grafting in chick (homeotic transformation); Hoxb1 and GATA2 loss- and gain-of-function epistasis

    PMID:10381880 PMID:10556076

    Open questions at the time
    • Whether GATA2 is a direct HOXB1 target not shown
    • Mechanism by which identity controls axon trajectory left open
  9. 1999 Medium

    NMR studies refined the assembly mechanism, showing the PBX1 fourth helix folds only on DNA and HOXB1 alone does not trigger it, indicating the ternary complex assembles cooperatively on DNA.

    Evidence Multidimensional NMR of free and bound PBX1 DNA-binding domain

    PMID:10448033

    Open questions at the time
    • Model not validated by mutagenesis
    • Single lab
  10. 2000 Medium

    Showed Hoxb1 patterns the entire dorsoventral axis of r4 by specifying Shh and Mash1 pathway effectors, broadening its role from migration to progenitor patterning and survival.

    Evidence Hoxb1 knockout with SHH/Mash1 pathway expression analysis

    PMID:11076756

    Open questions at the time
    • Direct versus indirect control of pathway effectors not distinguished
    • Single lab
  11. 2001 Medium

    Mapped a SOX/OCT context element in the autoregulatory enhancer and localized HOXB1's stronger transactivation to its N-terminal domain, explaining neuroectoderm-specific and paralog-specific activity.

    Evidence Reporter assays in EC cells, transgenic mice, Hoxa1 mutant analysis, domain mapping; NMR of preformed hexapeptide turn

    PMID:11278854 PMID:11369863

    Open questions at the time
    • Coactivators recruited by the N-terminal domain not identified
    • Hexapeptide preorganization shown only on isolated peptide
  12. 2003 High

    Structurally defined the SOX2/OCT1 partnership on the Hoxb1 element and showed re-specification of r4 neurons toward r2 identity in mutants, linking enhancer architecture to neuronal fate.

    Evidence Solution NMR of Oct1·Sox2·Hoxb1-DNA complex; Hoxb1 knockout with apoptosis block, markers, and DiI tracing

    PMID:14522873 PMID:14559893

    Open questions at the time
    • How re-specified neurons trigger apoptosis not mechanistically resolved
  13. 2004 High

    Revealed a non-neuronal requirement: Hoxb1 in r4-derived neural crest (Schwann cells) is needed to maintain VIIth nerve circuitry, separating specification from maintenance functions.

    Evidence Conditional Cre/loxP deletion in neural crest with lineage analysis and cultures

    PMID:15198977

    Open questions at the time
    • Crest-cell HOXB1 transcriptional targets not identified
    • Single lab
  14. 2005 High

    Dissected the autoregulatory enhancer into cooperative PH and PM (Prep1/Pbx/Meis) sites plus an inhibitory competing element, explaining how positive autoregulation is quantitatively restricted.

    Evidence In vitro binding and site-mutation transgenic reporters in chick and mouse

    PMID:16166636

    Open questions at the time
    • In vivo factor occupying the inhibitory site not definitively identified
  15. 2006 Medium

    Identified two repression mechanisms restricting Hoxb1 to r4: PIASxbeta/Krox20 regulation and direct Hoxb1 control of Hoxa2, clarifying how segment boundaries are enforced.

    Evidence Protein interaction and reporter assays (Krox20/PIASxbeta); in vitro binding, enhancer mutagenesis, and gain-of-function (Hoxa2)

    PMID:16675951 PMID:17113575

    Open questions at the time
    • PIASxbeta mechanism defined at domain level only, single lab
    • Direct contribution of Hoxa2 to r4 morphology not addressed
  16. 2008 Medium

    Connected Hoxb1 to progenitor self-renewal, showing it sustains posterior neural progenitor proliferation through Notch activation and Notch-dependent STAT3 Ser727 phosphorylation.

    Evidence Inducible Hoxb1 in ESC-derived neural stem cells with Notch and STAT3 phosphorylation assays

    PMID:18499896

    Open questions at the time
    • Direct transcriptional link between HOXB1 and Notch components not established
    • Single lab, in vitro system
  17. 2011 High

    Established direct negative regulation of Hoxb1 by Hoxb3 and identified a zebrafish target (ppp1r14al) linking Hoxb1 to the r4 FGF signaling center.

    Evidence EMSA, in vivo ChIP, reporter and gain-of-function for Hoxb3; ectopic expression and morpholino knockdown in zebrafish for ppp1r14al/fgf3

    PMID:21320481 PMID:21787765

    Open questions at the time
    • Whether ppp1r14al is a direct or indirect Hoxb1 target not fully resolved
  18. 2012 High

    Linked HOXB1 to human disease, showing a homodimer-destabilizing homeodomain missense mutation causes a bilateral facial palsy syndrome phenocopying the mouse knockout.

    Evidence Human genetics in affected families, molecular modeling, and in vitro DNA-binding of mutant protein

    PMID:22770981

    Open questions at the time
    • Full spectrum of human phenotypes and penetrance not defined
    • Quantitative effect on transcriptional output not measured
  19. 2015 High

    Expanded the organismal roles of Hoxb1 to vestibulospinal tract formation and to outflow tract cardiac development via control of FGF/ERK and BMP/SMAD signaling.

    Evidence Lineage tracing and knockouts with neuronal tracing/behavior (vestibulospinal); conditional and compound Hoxa1/Hoxb1 mutants with phospho-signaling analysis (heart)

    PMID:26284287 PMID:26730404

    Open questions at the time
    • Direct cardiac transcriptional targets not identified
    • Tissue-autonomous mechanism in vestibulospinal neurons not fully dissected
  20. 2021 High

    Genome-wide binding redefined HOXB1 as a dual activator/repressor, revealing predominant co-occupancy with REST and a novel HB1RE repressive motif rather than constitutive PBX/MEIS-activating sites.

    Evidence ChIP-seq in ESC-derived neural cells, in vitro template binding, and reporter assays

    PMID:33546292

    Open questions at the time
    • Physiological repressive target genes not functionally validated in vivo
    • How HOXB1 switches between REST and PBX/MEIS partnerships unknown
  21. 2023 High

    Pinpointed the cellular origin of HOXB1-dependent deafness to efferent olivocochlear motor neurons, distinguishing motor from sensory requirements.

    Evidence Cell-type-specific conditional Cre/loxP knockouts with auditory thresholds and immunohistochemistry

    PMID:37738262

    Open questions at the time
    • Downstream effectors of HOXB1 in olivocochlear neurons not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unknown how HOXB1 mechanistically toggles between PBX/MEIS-dependent activation and REST-associated repression, and which repressive targets mediate its developmental functions.
  • No structural or biochemical basis for the activation/repression switch
  • Repressive in vivo target genes uncharacterized
  • Link between genome-wide binding and specific neuronal phenotypes incomplete

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140110 transcription regulator activity 5 GO:0003677 DNA binding 4
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1266738 Developmental Biology 6 R-HSA-74160 Gene expression (Transcription) 5
Partners
HOXA1HOXB3MEISOCT1PBX1PREP1RESTSOX2
Complex memberships
HOXB1-PBX1-DNA ternary complexOct1-Sox2-Hoxb1-DNA complexPrep1-Pbx1-Hoxb1 complex

Evidence

Reading pass · 34 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 HOXB1 autoregulatory expression in rhombomere 4 requires cooperative binding with PBX/EXD cofactors to conserved sequence motifs in the r4 enhancer; in vitro binding of HOXB1 to these elements requires PBX1 as a cofactor, and in vivo r4 expression depends on both labial-family Hox members and exd in Drosophila, establishing a direct autoregulatory loop. In vitro DNA binding assays, transgenic mice reporter analysis, Drosophila transgenic embryo assays Cell High 7600572
1994 A conserved retinoic acid response element (RARE) located 3' of Hoxb-1 is essential for early expression in neuroectoderm and mediates the ectopic response to retinoic acid; point mutations in the RARE abolish neuroectoderm expression in transgenic mice. Transgenic mouse reporter analysis with RARE point mutations; cross-species functional conservation assay (mouse, chick, Fugu) Nature High 7914354
1994 A conserved RARE in the Hoxb-1 gene acts as a repressor to restrict expression to r4; point mutations in the RARE allow expression to spread into r3 and r5, demonstrating retinoids participate in sharpening segment-restricted Hoxb-1 expression. Transgenic mouse analysis, deletion and point mutation analysis of chick and mouse Hoxb-1 regulatory regions Science High 7916164
1996 Targeted disruption of Hoxb-1 (homeodomain and first exon) causes failure to form the somatic motor component of the VIIth (facial) nerve, demonstrating Hoxb1 is required for specification of facial branchiomotor neurons. Gene targeting in mice (two independent alleles), histological and neuroanatomical analysis Development High 8898234 8967950
1996 Loss of Hoxb-1 changes r4 identity: molecular markers show r4 patterning is initiated but not maintained; DiI tracing reveals facial branchiomotor (FBM) and CVA neurons fail to migrate to proper positions, instead forming an ectopic motor nucleus, demonstrating Hoxb1 controls migratory properties of motor neurons. Targeted gene knockout in mice, DiI lineage tracing, molecular marker analysis Nature High 8967950
1999 Crystal structure (2.35 Å) of a HoxB1-Pbx1 heterodimer bound to DNA reveals that heterodimer contacts are mediated by the HoxB1 hexapeptide inserting into a hydrophobic pocket in Pbx1 formed by a three-amino acid insertion; Pbx1 contains an additional alpha helix contributing to HoxB1 hexapeptide binding and stable DNA binding. X-ray crystallography of ternary complex Cell High 10052460
1997 Hoxb1 directly cross-regulates Hoxb2 expression in r4 through a bipartite Hox/Pbx binding motif in the Hoxb2 r4 enhancer; Hoxb1 cooperatively binds this site in a Pbx/Exd-dependent manner in vitro, and the endogenous Hoxb2 gene is no longer upregulated in r4 in Hoxb1 homozygous mutant embryos. Transgenic mouse deletion analysis, in vitro DNA binding, Drosophila transgenic assay, Hoxb1 knockout analysis Genes & development High 9242495
1998 HOXA1 and HOXB1 proteins, in complex with Pbx1, bind to Hox-Pbx consensus sites in the EphA2 (Eck) r4 enhancer in vitro and co-expression of either HOXA1 or HOXB1 with Pbx1 transactivates EphA2 enhancer-dependent reporter expression, demonstrating direct transcriptional regulation of EphA2 by these Hox proteins. In vitro DNA binding (EMSA), reporter transactivation assays, transgenic mouse analysis, Hoxa1/Hoxb1 double mutant analysis The Journal of biological chemistry High 9733765
1998 A DR5 RARE in the Hoxb-1 3' RAIDR5 enhancer is required for Hoxb-1 expression in the developing foregut (esophagus, lung, stomach, liver, pancreas) in transgenic mice; point mutations in the DR5 RARE abolish gut expression while rhombomere 4 expression is maintained. Transgenic mouse reporter analysis with specific RARE point mutations and enhancer deletions Development High 9671595
1995 The HOXB1 promoter contains an RA-responsive element composed of a DR-2 sequence (direct target of RAR/RXR heterodimer) plus a motif for an RA-inducible tissue-specific coactivator (retinoid-inducible protein); together these form a tripartite cascade potentiated by a proximal HOXB1 autoregulatory site. Reporter gene assays, identification of RAR/RXR binding to DR-2 element, identification of RA-inducible coactivator binding Proceedings of the National Academy of Sciences Medium 7831296
1995 A second, distinct RA-responsive site in the 3' region of HOXB1 contains a DR-2-type RAR/RXR binding site and a binding site for a distinct RA-dependent coactivator (retinoid-activating protein) with different tissue specificity from the 5' site, demonstrating HOXB1 activation through two distinct RA pathways. Reporter gene assays, identification of RAR/RXR binding to DR-2B element, tissue-specific coactivator binding Proceedings of the National Academy of Sciences Medium 7831297
1999 The Pbx1 fourth alpha-helix is unfolded when Pbx1 is free in solution; DNA binding triggers folding of this helix, while mixing HoxB1 with Pbx1 in the absence of DNA produces no conformational change, suggesting stable HoxB1-Pbx1-DNA ternary complex assembles on DNA. Multidimensional NMR spectroscopy of Pbx1 DNA-binding domain free and bound Journal of molecular biology Medium 10448033
2001 The HoxB1 hexapeptide (TFDWMK) adopts a preformed turn structure in solution closely resembling its conformation in the HoxB1/Pbx1/DNA crystal structure, suggesting the hexapeptide is at least partially preorganized to interact with Pbx1. NMR structural analysis of synthetic hexapeptide Protein science Medium 11369863
2003 Solution NMR structure of the ternary 42 kDa Oct1·Sox2·Hoxb1-DNA complex reveals Sox2 and the Oct1 POU_S domain interact through a predominantly hydrophobic interface; Sox2 binding locks the Oct1 POU_S domain in a single orientation on the Hoxb1 regulatory element, increasing Oct1 site-specific DNA affinity. Solution NMR structure determination using residual dipolar couplings and rigid body/torsion angle dynamics The Journal of biological chemistry High 14559893
1999 Retroviral misexpression of Hoxb1 in a specific rhombomere in chick embryos causes homeotic transformation of that rhombomere identity, demonstrated by reorganization of motor axon projections, establishing Hoxb1 as a segment identity determinant. Retroviral misexpression combined with orthotopic grafting in chick embryos, motor axon projection analysis Science High 10381880
1999 GATA3 expression in ventral r4 is downstream of Hoxb1: absence of Hoxb1 abolishes GATA2 expression in r4, loss of GATA2 abolishes GATA3 expression, and ubiquitous Hoxb1 induces ectopic GATA2 and GATA3 in ventral r2/r3, establishing a Hoxb1→GATA2→GATA3 pathway in facial branchiomotor and CVA neuron specification. Hoxb1 knockout analysis, GATA2 knockout analysis, Hoxb1 gain-of-function in vivo Development High 10556076
2000 Hoxb1 controls dorsoventral progenitor patterning throughout the entire DV axis of r4 by acting early during hindbrain neurogenesis to specify effectors of sonic hedgehog and Mash1 signaling pathways; in the absence of Hoxb1, multiple neurons programmed within r4 undergo cell death instead. Hoxb1 targeted disruption analysis, expression studies of SHH and Mash1 pathway components Development Medium 11076756
2001 A bipartite SOX/OCT binding site within the Hoxb1 autoregulatory element (b1-ARE) confers neuroectodermal cell context-specific activity and is required for maximal HOX/PBX transcriptional activation; HOXB1 has higher transcriptional activity than its paralog HOXA1, with the determinants mapping to the HOXB1 N-terminal transcriptional activation domain; Hoxa1 is the primary mediator of the retinoic acid response of b1-ARE in vivo. Reporter gene assays in embryonal carcinoma cells, transgenic mouse analysis, Hoxa1 mutant analysis, domain mapping The Journal of biological chemistry Medium 11278854
2003 In Hoxb1 mutants, neurons derived from presumptive r4 territory are re-specified towards r2-like identity; migrating motoneurons resemble trigeminal (r2) motoneurons in migration pattern and molecular marker expression, and ectopic nuclei form that are subsequently cleared by apoptosis (survival extended by blocking apoptosis). Hoxb1 knockout combined with apoptosis pathway block, molecular marker analysis, DiI tracing Development High 14522873
2004 Hoxb1 is required not only in r4 motoneurons but also in r4-derived neural crest to facilitate and maintain VIIth cranial nerve circuitry; conditional deletion in neural crest shows neural crest-derived glial cells (Schwann cells) that myelinate the VIIth nerve require Hoxb1 for nerve maintenance, while overall glial progenitor specification is unaffected. Conditional Cre/loxP deletion in neural crest, genetic lineage analysis, neural crest cultures Genes & development High 15198977
2005 The Hoxb1 autoregulatory enhancer contains both Pbx-Hoxb1 (PH) and Pbx-Meis/Prep1 (PM) binding sites; a new PM2 site cooperates with R3 PH site to form ternary Prep1-Pbx1-Hoxb1 complexes; the R2/PM3 motif acts as an inhibitory element by competing for Prep1-Pbx1 binding and reducing/restricting reporter expression in transgenic embryos. In vitro binding assays, transgenic chick and mouse reporter analysis with site mutations Molecular and cellular biology High 16166636
2006 PIASxbeta directly interacts with Krox20 (zinc-finger transcription factor) and independently activates Hoxb1 expression; Krox20 binding to PIASxbeta through its zinc-finger domain prevents this activation, providing a molecular mechanism for Krox20-mediated repression of Hoxb1 in r3/r5. Protein-protein interaction assays, reporter gene assays, domain mapping of Krox20 The EMBO journal Medium 16675951
2006 Hoxa2 expression in r4 is directly regulated by Hoxb1: three bipartite Hox/Pbx sites (PH1-PH3) and one Pbx-Prep/Meis (PM) site in the Hoxa2 intron r4 enhancer cooperate for enhancer activity; ectopic HOXB1 induces expression from this enhancer in vivo, establishing Hoxa2 as a direct Hoxb1 target gene. In vitro DNA binding, mutational analysis of enhancer sites, transgenic mouse and chick analysis, Hoxb1 gain-of-function Developmental biology High 17113575
2008 Hoxb1 mediates maintenance and expansion of posterior neural progenitor cells; Hoxb1+ cells continue proliferating upon mitogen withdrawal through Hoxb1-dependent activation of Notch signaling and Notch-dependent STAT3 phosphorylation at Ser727, linking Hox gene function with JAK/STAT pathway maintenance. Transgenic Hoxb1 induction in ESC-derived neural stem cells, Notch pathway analysis, STAT3 phosphorylation assays Stem cells Medium 18499896
2011 Hoxb3 directly represses Hoxb1 transcription: a Hoxb3 binding site (S3) was identified on the Hoxb1 locus; Hoxb3 protein binds S3 in vitro (EMSA) and in vivo (ChIP in hindbrain tissue and P19 cells); Hoxb3 suppresses Hoxb1 transcriptional activity in a luciferase reporter assay; ectopic Hoxb3 in r4 abolishes Hoxb1 expression and phenocopies Hoxb1 loss. EMSA, in vivo ChIP, luciferase reporter assay, transgenic gain-of-function mouse Developmental biology High 21320481
2011 Hoxb1b (zebrafish) directly regulates ppp1r14al expression in rhombomere 4, and ppp1r14al is essential for establishment of the r4 Fgf signaling center by regulating fgf3 expression. Ectopic expression screen in zebrafish embryos, morpholino knockdown, in situ hybridization Developmental biology Medium 21787765
2012 A human HOXB1 founder missense mutation (Arg207Cys, corresponding to Arg5 of the homeodomain) disrupts hydrogen bonding and electrostatic interactions with thymine in the DNA minor groove, destabilizing the HOXB1:PBX1:DNA complex and altering HOXB1 transcriptional activity, causing bilateral facial palsy phenotype recapitulating Hoxb1-/- mice. Molecular modeling, in vitro DNA-protein binding assay, human genetics (homozygous missense in affected families) American journal of human genetics High 22770981
2015 Hoxb1 deficiency in pharyngeal mesoderm results in a shorter outflow tract and ventricular septal defects due to enhanced FGF/ERK and BMP/SMAD signaling and premature myocardial differentiation; Hoxa1 and Hoxb1 have redundant roles during outflow tract development as shown by compound mutant analysis. Hoxb1 conditional and null knockout in mice, compound Hoxa1/Hoxb1 mutant analysis, signaling pathway analysis (phospho-ERK, phospho-SMAD) Developmental biology Medium 26284287
2015 R4-derived neurons marked by the Hoxb1 enhancer constitute essentially all LVST neurons; in Hoxb1-null mice, r4-derived LVST and cMVST subpopulations fail to form and r4-derived reticulospinal neurons are depleted, demonstrating Hoxb1 is required for developmental patterning of the vestibulospinal system. Transgenic mouse lineage tracing (Hoxb1-enhancer-driven reporter), Hoxb1-null knockout, retrograde neuronal tracing, behavioral analysis eNeuro High 26730404
2021 Genome-wide ChIP analysis of HOXB1 in ESC-derived neural cells reveals only 7% of HOXB1 binding peaks correlate with PBX/MEIS co-occupancy (active marks), while 22% co-occupy with transcriptional repressor REST (repressive marks); a novel 15 bp HOXB1 binding motif (HB1RE) was identified, and in vitro template binding shows HOXB1, PBX1, and MEIS bind this motif; overexpression of HOXB1 selectively represses reporter activity driven by HB1RE. Genome-wide ChIP-seq, in vitro template binding assay, reporter gene assay Journal of developmental biology High 33546292
2009 Lrrn2 expression in r4 branchiomotor neurons acts downstream of Hoxb1 and Shh; combined misexpression of Hoxb1 and Shh induces ectopic Lrrn2 in r1/2; misexpression of Lrrn2 in r2/3 redirects axonal projections to the r4 exit point, demonstrating Lrrn2 is a Hoxb1 downstream effector for motor axon guidance. In ovo electroporation misexpression, axon tracing in chick embryos Neural development Medium 19602272
2022 In neuromesodermal progenitors, Hoxb1 promotes cell survival through upregulation of Fgf8, Fgf17, and other FGF signaling components and repression of apoptotic pathway components; in hindbrain neural progenitors, Hoxb1 synergizes with Shh to direct specification of facial branchiomotor neuron (FBM)-like progenitors and upregulates Ret tyrosine kinase receptor expression. ESC-derived neuromesodermal progenitor and hindbrain progenitor differentiation, Hoxb1 inducible transgene, RNA-seq, pathway analysis Stem cells Medium 35257173
2023 Hoxb1-dependent sensorineural hearing loss is caused primarily by defective efferent motor neuron innervation of outer hair cells: conditional inactivation of Hoxb1 specifically in efferent motor neurons (not sensory cochlear neurons) reproduces the hearing phenotype, demonstrating Hoxb1 is required in olivocochlear motor neurons for establishment of normal cochlear innervation and hair cell survival. Conditional Cre/loxP knockout in specific neuron populations, auditory threshold measurement, immunohistochemistry PLoS genetics High 37738262
1998 HOXB1, HOXB2, and HOXB3 proteins bind to a conserved palindromic TAATTA-containing sequence in the upstream region of the Otx2 gene and positively regulate an Otx2 reporter in embryonal carcinoma cells; the HOXB1/HOXB3 binding region is required to mediate this up-regulation. Reporter gene co-transfection assay, EMSA with nuclear extracts and recombinant protein, deletion analysis The Journal of biological chemistry Medium 9556594

Source papers

Stage 0 corpus · 76 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Segmental expression of Hoxb-1 is controlled by a highly conserved autoregulatory loop dependent upon exd/pbx. Cell 443 7600572
1994 A conserved retinoic acid response element required for early expression of the homeobox gene Hoxb-1. Nature 390 7914354
1996 Altered segmental identity and abnormal migration of motor neurons in mice lacking Hoxb-1. Nature 344 8967950
1999 Structure of a HoxB1-Pbx1 heterodimer bound to DNA: role of the hexapeptide and a fourth homeodomain helix in complex formation. Cell 280 10052460
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
1994 Role of a conserved retinoic acid response element in rhombomere restriction of Hoxb-1. Science (New York, N.Y.) 246 7916164
1996 Mice with targeted disruption of Hoxb-1 fail to form the motor nucleus of the VIIth nerve. Development (Cambridge, England) 244 8898234
1997 Cross-regulation in the mouse HoxB complex: the expression of Hoxb2 in rhombomere 4 is regulated by Hoxb1. Genes & development 171 9242495
1999 Mice mutant for both Hoxa1 and Hoxb1 show extensive remodeling of the hindbrain and defects in craniofacial development. Development (Cambridge, England) 163 10529420
2002 Knockdown of duplicated zebrafish hoxb1 genes reveals distinct roles in hindbrain patterning and a novel mechanism of duplicate gene retention. Development (Cambridge, England) 156 11973267
2003 Molecular basis for synergistic transcriptional activation by Oct1 and Sox2 revealed from the solution structure of the 42-kDa Oct1.Sox2.Hoxb1-DNA ternary transcription factor complex. The Journal of biological chemistry 135 14559893
1999 Homeotic transformation of rhombomere identity after localized Hoxb1 misexpression. Science (New York, N.Y.) 120 10381880
1996 Targeted disruption of the Hoxb-2 locus in mice interferes with expression of Hoxb-1 and Hoxb-4. Development (Cambridge, England) 120 9012503
2000 Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders. Teratology 110 11091361
2006 Genome-wide scanning of HoxB1-associated loci in mouse ES cells using an open-ended Chromosome Conformation Capture methodology. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology 109 16823611
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 A conserved retinoic acid responsive element in the murine Hoxb-1 gene is required for expression in the developing gut. Development (Cambridge, England) 94 9671595
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
1999 The transcription factor GATA3 is a downstream effector of Hoxb1 specification in rhombomere 4. Development (Cambridge, England) 87 10556076
2005 Hoxb1 enhancer and control of rhombomere 4 expression: complex interplay between PREP1-PBX1-HOXB1 binding sites. Molecular and cellular biology 74 16166636
1995 A retinoic acid-triggered cascade of HOXB1 gene activation. Proceedings of the National Academy of Sciences of the United States of America 73 7831296
2000 Mechanisms of Hox gene colinearity: transposition of the anterior Hoxb1 gene into the posterior HoxD complex. Genes & development 70 10652274
2011 MeCP2 is critical within HoxB1-derived tissues of mice for normal lifespan. The Journal of neuroscience : the official journal of the Society for Neuroscience 66 21753013
2006 Expression of Hoxa2 in rhombomere 4 is regulated by a conserved cross-regulatory mechanism dependent upon Hoxb1. Developmental biology 66 17113575
1995 Evidence for two distinct retinoic acid response pathways for HOXB1 gene regulation. Proceedings of the National Academy of Sciences of the United States of America 63 7831297
2012 HOXB1 founder mutation in humans recapitulates the phenotype of Hoxb1-/- mice. American journal of human genetics 61 22770981
2000 Hoxb1 controls effectors of sonic hedgehog and Mash1 signaling pathways. Development (Cambridge, England) 59 11076756
2002 Analysis of two distinct retinoic acid response elements in the homeobox gene Hoxb1 in transgenic mice. Developmental dynamics : an official publication of the American Association of Anatomists 58 11891985
2000 A large targeted deletion of Hoxb1-Hoxb9 produces a series of single-segment anterior homeotic transformations. Developmental biology 58 10885747
1996 Rescue of Drosophila labial null mutant by the chicken ortholog Hoxb-1 demonstrates that the function of Hox genes is phylogenetically conserved. Genes & development 58 8566751
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
2004 Hoxb1 functions in both motoneurons and in tissues of the periphery to establish and maintain the proper neuronal circuitry. Genes & development 49 15198977
2003 Hoxb1 neural crest preferentially form glia of the PNS. Developmental dynamics : an official publication of the American Association of Anatomists 48 12815623
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
1997 The role of planar and early vertical signaling in patterning the expression of Hoxb-1 in Xenopus. Developmental biology 39 9133441
2008 Hoxb1 controls cell fate specification and proliferative capacity of neural stem and progenitor cells. Stem cells (Dayton, Ohio) 34 18499896
2008 Ectopic nuclear reorganisation driven by a Hoxb1 transgene transposed into Hoxd. Journal of cell science 33 18252796
2002 Lack of association between HoxA1 and HoxB1 gene variants and autism in 110 multiplex families. American journal of medical genetics 32 11840501
2015 HOXB1 Is a Tumor Suppressor Gene Regulated by miR-3175 in Glioma. PloS one 31 26565624
1999 NMR studies of the pbx1 TALE homeodomain protein free in solution and bound to DNA: proposal for a mechanism of HoxB1-Pbx1-DNA complex assembly. Journal of molecular biology 27 10448033
2016 Hoxa1 and Hoxb1 are required for pharyngeal arch artery development. Mechanisms of development 26 27956219
2015 Loss of Projections, Functional Compensation, and Residual Deficits in the Mammalian Vestibulospinal System of Hoxb1-Deficient Mice. eNeuro 25 26730404
2012 Hoxb1 controls anteroposterior identity of vestibular projection neurons. PloS one 25 22485187
2011 A screen for hoxb1-regulated genes identifies ppp1r14al as a regulator of the rhombomere 4 Fgf-signaling center. Developmental biology 24 21787765
2016 Homozygous HOXB1 loss-of-function mutation in a large family with hereditary congenital facial paresis. American journal of medical genetics. Part A 22 27144914
2018 Hsa-let-7g promotes osteosarcoma by reducing HOXB1 to activate NF-kB pathway. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 21 30551492
2001 The HoxB1 hexapeptide is a prefolded domain: implications for the Pbx1/Hox interaction. Protein science : a publication of the Protein Society 20 11369863
2013 HOXB1 restored expression promotes apoptosis and differentiation in the HL60 leukemic cell line. Cancer cell international 17 24148231
2011 Hoxb3 negatively regulates Hoxb1 expression in mouse hindbrain patterning. Developmental biology 17 21320481
2010 Tethered-hopping model for protein-DNA binding and unbinding based on Sox2-Oct1-Hoxb1 ternary complex simulations. Biophysical journal 17 20371328
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
1998 Regulatory interactions between the human HOXB1, HOXB2, and HOXB3 proteins and the upstream sequence of the Otx2 gene in embryonal carcinoma cells. The Journal of biological chemistry 16 9556594
2020 The MicroRNA hsa-let-7g Promotes Proliferation and Inhibits Apoptosis in Lung Cancer by Targeting HOXB1. Yonsei medical journal 15 32102121
2021 MicroRNA-301b-3p facilitates cell proliferation and migration in colorectal cancer by targeting HOXB1. Bioengineered 14 34488545
2006 PIASxbeta acts as an activator of Hoxb1 and is antagonized by Krox20 during hindbrain segmentation. The EMBO journal 14 16675951
2018 Ectopic expression of Hoxb1 induces cardiac and craniofacial malformations. Genesis (New York, N.Y. : 2000) 13 30134070
2021 Genome-Wide Binding Analyses of HOXB1 Revealed a Novel DNA Binding Motif Associated with Gene Repression. Journal of developmental biology 10 33546292
2009 Chick Lrrn2, a novel downstream effector of Hoxb1 and Shh, functions in the selective targeting of rhombomere 4 motor neurons. Neural development 10 19602272
2007 Consequences of hoxb1 duplication in teleost fish. Evolution & development 10 17976051
2016 A novel homozygous HOXB1 mutation in a Turkish family with hereditary congenital facial paresis. Brain & development 8 27640920
2015 Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice. Genetics 8 26447130
1998 The murine Hoxb1 3' RAIDR5 enhancer contains multiple regulatory elements. Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research 8 9869297
2010 Candidate gene study of HOXB1 in autism spectrum disorder. Molecular autism 6 20678259
1998 A genetic polymorphism in the human HOXB1 homeobox gene implying a 9bp tandem repeat in the amino-terminal coding region. Mutations in brief no. 200. Online. Human mutation 6 10671062
1996 Expression of Hoxb-1 during gastrulation and segmentation stages of carp (Cyprinus carpio). The International journal of developmental biology 6 8793616
2017 A Novel Loss-of-Function Mutation in HOXB1 Associated with Autosomal Recessive Hereditary Congenital Facial Palsy in a Large Iranian Family. Molecular syndromology 5 28878610
2000 The previously identified r3/r5 repressor may require the cooperation of additional negative elements for rhombomere restriction of Hoxb1. Brain research. Developmental brain research 4 10775768
2022 Hoxb1 Regulates Distinct Signaling Pathways in Neuromesodermal and Hindbrain Progenitors to Promote Cell Survival and Specification. Stem cells (Dayton, Ohio) 3 35257173
2022 Transgenic human HOXB1-9 directs anterior-posterior axial skeleton pattern in Hoxb1-9 deficient mice. Differentiation; research in biological diversity 3 36041259
2024 Retinoic Acid Regulates Spermiogenesis Via Hoxb1 and Shh Signaling in Testicular Germ Cells. Reproductive sciences (Thousand Oaks, Calif.) 2 39080234
2024 Two novel compound heterozygous HOXB1 variants in congenital facial palsy: A case report and a brief review of the literature. American journal of medical genetics. Part A 1 39235314
2023 Abnormal outer hair cell efferent innervation in Hoxb1-dependent sensorineural hearing loss. PLoS genetics 1 37738262
2018 Analysis of HOXB1 gene in a cohort of patients with sporadic ventricular septal defect. Molecular biology reports 1 29923154
2001 [Influence of human cytomegalovirus infection on the expressions of HOXB1, HOXB5, HOXB6, and HOXB9 genes in human embryo lung cells]. Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 0 12536675

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