| 1997 |
HOXB3 overexpression in murine bone marrow cells via retroviral gene transfer caused defective lymphoid development (reduced CD4+CD8+ thymocytes, absent IL-7-responsive pre-B progenitors) and progressive myeloproliferation (elevated granulocyte macrophage colony-forming cells), establishing a direct role for HOXB3 in hematopoietic proliferation and differentiation. |
Retroviral gene transfer into murine bone marrow; transplantation into mice; flow cytometry and colony assays |
Immunity |
High |
9052833
|
| 1997 |
The kreisler protein (Krml1), a Maf/bZIP transcription factor expressed in rhombomeres 5 and 6, directly binds two conserved sequence blocks (19 bp and 45 bp) in the Hoxb3 r5 enhancer and activates Hoxb3 transcription in r5, with an Ets-related activation site also required for both activation and r5 restriction. |
Transgenic reporter analysis; in vitro binding assays; deletion/mutational analysis of enhancer elements |
Nature |
High |
9144291
|
| 1999 |
Hoxa3, like its paralog Hoxb3, is a direct transcriptional target of kreisler (Krml1) in the hindbrain; a single high-affinity Krml1 binding site in the Hoxa3 r5/r6 enhancer is necessary and sufficient for kreisler-dependent activation, but the number and arrangement of binding sites differ between Hoxa3 and Hoxb3 enhancers, accounting for their distinct segmental restriction (r5/r6 vs. r5 only). |
Transgenic analysis; deletion analysis; ectopic kreisler expression; kreisler-null embryo analysis |
Development |
High |
9895323
|
| 1998 |
HOXB3-induced cellular transformation and proliferation of Rat-1 cells requires cooperation with PBX1; the conserved tetrapeptide (mediating PBX binding) and homeodomain (mediating DNA binding) are both required for transforming activity, and modulating PBX1 levels strongly modulates HOXB3 transforming capacity. |
Rat-1 cell transformation assay; co-transfection with PBX1; deletion/point mutations of tetrapeptide and homeodomain |
Oncogene |
High |
9692548
|
| 1998 |
HOXB1, HOXB2, and HOXB3 proteins all positively regulate a 534-bp upstream fragment of the Otx2 gene in embryonal carcinoma cells; HOXB3 (homeodomain-containing bacterial extract) binds to palindromic TAATTA sites within this fragment, and this binding region is necessary for Otx2 up-regulation. |
Co-transfection reporter assay; EMSA with recombinant HOXB3 homeodomain; nuclear extract binding assays |
Journal of Biological Chemistry |
Medium |
9556594
|
| 2002 |
Krox20 (expressed in r3 and r5) is required for activity of the Hoxb3 r5 enhancer (but not the Hoxa3 r5/r6 enhancer); Krox20 binds the Hoxb3 r5 enhancer and synergizes with kreisler to restrict expression to r5 (the overlap domain of both factors), as shown by genetic analysis in Krox20-null embryos and ectopic Krox20 expression. |
Genetic analysis (Krox20-null mice); ectopic expression; mutational analysis of enhancer; EMSA |
EMBO Journal |
High |
11823429
|
| 2001 |
Multiple widely-spaced cis-acting regulatory elements (Ib, IIIa, IVa, IVb, Va) within and flanking the Hoxb3 locus control distinct tissue- and stage-specific expression domains in a modular, additive manner; element IVa (r5 enhancer) controls anterior neural expression in r5, element IIIa directs anterior spinal cord/hindbrain to r6, region A/element I mediates posterior neural expression, and element Va controls mesoderm-specific expression. |
Transgenic lacZ reporter analysis with multiple DNA fragments; combinatorial element testing |
Developmental Biology |
Medium |
11254356
|
| 2002 |
Hoxb3 auto/cross-regulates its own expression in the neural tube: within the 482-bp element IIIa, two Hox binding sites are bound in vitro by both Hoxb3 and Hoxb4 proteins; a novel GCCAGGC motif is also required; kreisler binding sites in this element are not required for r6 or neural crest expression. |
Transgenic analysis; in vitro binding (EMSA); deletion/mutational analysis of element IIIa |
Developmental Biology |
Medium |
12482716
|
| 2003 |
Mice deficient in both Hoxb3 and Hoxb4 display reduced hematopoietic stem cell (HSC) pool in fetal liver, diminished progenitor numbers, impaired proliferative capacity of Lin-Sca1+c-kit+ progenitors in vitro, reduced in vivo repopulating capability, and slower cell cycle kinetics without perturbing lineage commitment, indicating that Hoxb3 and Hoxb4 cooperate to regulate HSC proliferation and self-renewal. |
Double-knockout mouse model; competitive repopulation assay; in vitro colony assay; flow cytometry; cytostatic drug treatment |
Molecular and Cellular Biology |
High |
12748289
|
| 2000 |
The Polycomb group protein rae28 is required for maintenance (but not establishment) of Hoxb3 expression boundaries; rae28-deficient mice show ectopic anterior extension of Hoxb3 expression in hindbrain and pharyngeal arch despite normal kreisler and Krox20 expression, indicating rae28 restricts Hoxb3 expression domain post-establishment. |
rae28-knockout mouse analysis; in situ hybridization for Hoxb3, kreisler, Krox20, p75; temporal expression analysis |
Mechanisms of Development |
Medium |
11044623
|
| 2005 |
The Hoxb3 cis-element b3IIIa functions as a vagal neural crest-specific enhancer that directs expression in vagal (but not trunk or sacral) neural crest, marks a subset of enteric neuroblasts, and is maintained in differentiated myenteric plexus neurons; in Dom mutant mice (Hirschsprung's model), colonization of b3IIIa-expressing cells in large intestine was incomplete. |
Transgenic lacZ reporter analysis; cellular marker co-localization; genetic cross with Dom mutant mice |
Developmental Dynamics |
Medium |
15768390
|
| 2007 |
Hoxb3-deficient mice develop age-dependent impairment of B lymphopoiesis: by 6 months, Hoxb3-/- mice show reduced BM cellularity, twofold reduction in B220+CD43+ progenitor B cells, fivefold reduction in B220+CD43-IgM- precursor B cells, reduced IL-7 receptor expression on progenitor B cells, and impaired IL-7-driven proliferation in vitro. |
Hoxb3 knockout mouse analysis; flow cytometry; in vitro IL-7 stimulation proliferation assay; IL-7R expression analysis |
Experimental Hematology |
High |
17309827
|
| 2009 |
HOXB3 epigenetically silences RASSF1A tumor suppressor by binding to and transcriptionally activating the DNMT3B promoter; DNMT3B is then recruited to the RASSF1A promoter via interactions with Polycomb repressor complex 2 and MYC, resulting in hypermethylation and silencing of RASSF1A; HOXB3 oncogenic activity in xenograft models is partly dependent on RASSF1A silencing. |
Genome-wide shRNA screen; ChIP; bisulfite sequencing; reporter assays; shRNA knockdown; mouse xenograft experiments |
Molecular Cell |
High |
19854132
|
| 2011 |
Hoxb3 directly represses Hoxb1 transcription by binding to a novel site S3 on the Hoxb1 locus; EMSA confirmed protein-DNA interaction in vitro; in vivo ChIP in P19 cells and hindbrain tissues from Hoxb3(Tg) mutant confirmed occupancy; luciferase reporter assay in chick demonstrated transcriptional suppression; in wildtype E10.5 caudal hindbrain (where Hoxb1 is absent), Hoxb3 occupies the S3 site. |
EMSA; in vivo ChIP; luciferase reporter assay (chick in ovo); gain-of-function transgenic mouse |
Developmental Biology |
High |
21320481
|
| 2012 |
HoxB3 promotes prostate cancer cell proliferation and migration by transcriptionally activating CDCA3; ChIP analysis showed HoxB3 binds the CDCA3 promoter; depletion of HoxB3 decreased proliferation in a CDCA3-dependent manner both in vitro and in vivo. |
ChIP; shRNA knockdown; overexpression; xenograft in vivo; proliferation/migration assays |
Cancer Letters |
Medium |
23219899
|
| 2015 |
HOXB3 overexpression in mouse pro-B cells decreased FLT3-ITD-dependent cell proliferation and colony formation, increased apoptosis, and significantly reduced FLT3-ITD-induced phosphorylation of AKT, ERK, p38, and STAT5, indicating HOXB3 acts as a suppressor of FLT3-ITD oncogenic signaling. |
Overexpression in mouse pro-B cells; colony formation assay; Western blot for phospho-AKT, phospho-ERK, phospho-p38, phospho-STAT5; apoptosis assay |
Biochemical and Biophysical Research Communications |
Medium |
26482852
|
| 2018 |
HOXB3 drives leukemogenesis partly by transcriptionally activating CDCA3 (confirmed by knockdown reducing CDCA3 and cell proliferation) and inducing DNMT3B expression; DNMT3B then methylates the pre-miR-375 promoter to silence miR-375, creating a HOXB3→DNMT3B→miR-375 feedback loop that sustains HOXB3 expression; miR-375 directly targets HOXB3 3'-UTR (luciferase reporter). |
Luciferase reporter assay for miR-375/HOXB3 3'-UTR; shRNA knockdown; colony formation; xenograft; bisulfite sequencing of pre-miR-375 promoter |
BMC Cancer |
Medium |
29439669
|
| 2021 |
Hoxb3 directly regulates Jag1 expression in pharyngeal epithelium: molecular experiments showed Hoxb3 binds to an upstream genomic site S2 on the Jag1 locus; ectopic Hoxb3 in Hoxb3(Tg) mutant specifically upregulated Jag1 in ectodermal pharyngeal epithelial cells of PA2; elevated Jag1 led to abnormal cellular interaction and deficiency of neural crest cells migrating into PA2. |
ChIP/molecular binding assay; gain-of-function transgenic mouse; in situ hybridization; cellular migration analysis |
Frontiers in Physiology |
Medium |
33505317
|
| 2023 |
In castration-resistant prostate cancer (CRPC), WNT3A signaling and APC deficiency cause HOXB3 to dissociate from the destruction complex and translocate to the nucleus, where it transcriptionally activates multiple WNT pathway genes; HOXB3 suppression reduced proliferation in APC-downregulated CRPC cells and re-sensitized APC-deficient CRPC xenografts to abiraterone. |
RNA sequencing; WNT3A treatment; APC knockdown; nuclear fractionation/localization; xenograft assays; proliferation assays |
Cell Death & Disease |
Medium |
36973255
|
| 2023 |
HOXB3 transcriptionally activates Notch1 by binding to its promoter (confirmed by luciferase reporter and ChIP assays); this promotes Wnt/β-catenin pathway activation and trophoblast cell proliferation, migration, and invasion; Notch1 knockdown abrogated HOXB3 functions in trophoblasts. |
Luciferase reporter assay; ChIP; siRNA knockdown; cell proliferation/migration/invasion assays; rat PE model |
European Journal of Pharmacology |
Medium |
37652291
|
| 2024 |
STUB1 (an E3 ubiquitin ligase) mediates ubiquitination and degradation of HOXB3; HOXB3 in turn transcriptionally activates PARK7 by binding to its promoter; the STUB1→HOXB3→PARK7 axis regulates ferroptosis and paclitaxel resistance in ovarian cancer cells. |
Co-immunoprecipitation; dual luciferase reporter assay; RT-qPCR; western blot; overexpression/knockdown rescue experiments; xenograft |
Communications Biology |
Medium |
39501077
|
| 2024 |
SIRT5 desuccinylates HOXB3 as a post-translational modification, suppressing HOXB3 activity; SIRT5 inhibition increases trophoblast proliferation, invasion, and migration through HOXB3-dependent Notch and β-catenin signaling pathway activation; silencing HOXB3 reversed these effects. |
Co-immunoprecipitation; dual-luciferase reporter assay; siRNA knockdown rescue; proliferation/invasion/migration assays in HTR-8/SVneo cells |
Journal of Assisted Reproduction and Genetics |
Medium |
39145876
|
| 2025 |
HOXB3 forms phase-separated condensates in a subset of glioblastoma cells through its intrinsically disordered regions and interactions with RUNX1; these condensates drive oncogenic transcription at super-enhancer-associated sites; a peptide (P621-R9) disrupting HOXB3 condensation altered chromatin structure, reduced super-enhancer-driven transcription, and selectively diminished tumorigenic potential in GBM patient-derived xenograft models with HOXB3 condensates. |
Single-cell CUT&Tag (H3K27ac); condensate/phase separation analysis; peptide disruption assay; patient-derived xenograft models; chromatin structure analysis |
Nature Cell Biology |
High |
41028837
|