Disease relevance of HOXB1

• Furthermore, we found that in an embryonal carcinoma cell background, HOXB1 has a significantly higher transcriptional activity than its paralog HOXA1 [1].
• It was determined that HOXB1, B3, B5, B6, B7, B8, and B9 genes are expressed in normal adult cervical epithelium and squamous cervical carcinomas [2].
• Concerted 5' ABL1 deletions in patient samples with a chromosome 9;22 translocation and chronic myelogenous leukemia were confirmed by comparison of the mean fluorescence intensities of ABL1 test probes with a HOXB1 reference probe [3].
• We investigated the expression and function of HOXB cluster genes in human melanoma [4].
• All of the mutants that survived to 3 weeks of age showed marked facial paralysis similar to, but more severe than, that reported for hoxb-1 mutant homozygotes (Goddard, J. M., Rossel, M., Manley, N. R. and Capecchi, M. R. (1996) Development 122, 3217-3228) [5].

High impact information on HOXB1

• Interaction with Prep1 enhances the ability of the HOXB1-Pbx1 complex to activate transcription in a cooperative fashion from the same target [6].
• Functional dissection of the complex allowed the localization of the main activation domain in the HOXB1 N-terminal region, and of an additional one in the C-terminal region of Pbx1 contained in the Pbx1a but not in the alternatively spliced Pbx1b isoform [7].
• Positional candidate genes that belong to the growth hormone and homeobox B gene clusters were excluded [8].
• These data define an unusual regulatory mechanism leading to the establishment of HOXB1 gene expression [9].
• A retinoic acid-triggered cascade of HOXB1 gene activation [10].

Chemical compound and disease context of HOXB1

• The expression patterns of the class I homeogenes HOXB and HOXC clusters in the presence of retinoic acid (RA) were studied in two human small-cell lung cancer (SCLC) cell lines and compared to that of NT2/D1 embryonal carcinoma cells [11].

Biological context of HOXB1

• We map the determinants for this differential activity within the HOXB1 N-terminal transcriptional activation domain [1].
• DNA binding assays and cell transfection experiments revealed that the bipartite core sequence of FPB (5'-ATCAATCA-3') binds the PBX1/2, PREP1, and HOXB1 proteins, and this in turn leads to promoter transactivation [12].
• We previously showed that HOXB1 and PBX1 activate transcription from the b1-ARE by binding to sequences required for the expression of a reporter gene in rhombomere 4 in vivo [1].
• 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 [13].
• Discovery of allelic variants of HOXA1 and HOXB1: genetic susceptibility to autism spectrum disorders [14].

Anatomical context of HOXB1

• We report that the human Pbx1 and HOXB1 proteins can cooperatively activate transcription through a genetically characterized Hox target, i.e. an autoregulatory element directing spatially restricted expression of the murine Hoxb-1 gene (b1-ARE) in the developing hindbrain [7].
• Next, we have attempted to identify the precise branchiomotor subtypes that are generated after misexpression and our results suggest that the ectopic motor neurons generated following Hoxa2 misexpression are trigeminal-like, while those generated following Hoxb1 misexpression are facial-like [15].
• As for the hoxb-1 mutations, the facial paralysis observed in mice homozygous for the hoxb-2 mutation results from a failure to form the somatic motor component of the VIIth (facial) nerve which controls the muscles of facial expression [5].
• Remarkably, within the hematopoietic compartment, genes of the HOXB complex are expressed specifically in erythromegakaryocytic cell lines and, for some of them, in hematopoietic progenitors [16].
• HOXB cluster genes in activated natural killer lymphocytes: expression from 3'-->5' cluster side and proliferative function [17].

Associations of HOXB1 with chemical compounds

• Evidence for two distinct retinoic acid response pathways for HOXB1 gene regulation [9].
• Through neither enhancer alone is functional, this combined element strongly activates the HOXB1 promoter in a cell-specific and retinoid-dependent manner [10].
• Several lines of evidence suggest that multiple genes of the HOXB (B2, B4, B6-B9), HOXC (C6, C8), and HOXA (A5) are involved in erythropoiesis [18].
• Recently, it has been shown that expression of human HOX 2 genes is sequentially activated by RA beginning from Hox 2.9 at the 3' end of the HOX 2 cluster (A. Simeone, D. Acampora, L. Arcioni, P. W. Andrews, E. Boncinelli, and F. Mavilio, Nature [London] 346:763-766, 1990) [19].

Physical interactions of HOXB1

• Expanded HOXA1 variants exhibited reduced PBX1-coupled transcriptional activity through a regulatory enhancer of HOXB1 [20].

Other interactions of HOXB1

• Similarly, overexpression of different combinations of PBX1, PREP1, and HOXB1 transactivates FPB-driven transcription [12].
• HOXB1, HOXB3, and nuclear extracts from 12.5 days postcoitum mouse embryos bind to a sequence containing two palindromic TAATTA sites, which bear four copies of the ATTA core sequence, a common feature of most HOM-C/HOX binding sites [21].
• Inhibition of retinoic acid-induced activation of 3' human HOXB genes by antisense oligonucleotides affects sequential activation of genes located upstream in the four HOX clusters [22].
• Here, we report the study of HOXB2 gene transcriptional regulation in hematopoietic cells, an initial step in understanding the lineage-specific expression of the whole HOXB complex in these cells [16].
• Thus, 1) a coordinate activation of HOXB genes from the 3'-->5' cluster side apparently underlies IL-2/IL-1 beta-induced NK cell activation [17].

Analytical, diagnostic and therapeutic context of HOXB1

• Reverse transcription-polymerase chain reaction analysis and nonradioactive RNA in situ hybridization were used to detect HOXB expression in 11 normal cervical tissues and 17 cervical carcinomas [2].
• We have also investigated the region-specific expression of HOX-2 genes in human embryonic-fetal life by Northern-blot analysis [23].
• We investigated the expression of HOXB cluster genes in purified phytohemagglutinin (PHA)-activated T lymphocytes from normal adult peripheral blood by reverse transcription PCR and RNase protection [24].
• We have investigated by reverse transcription-polymerase chain reaction (RT-PCR) the mRNA expression of homeobox B (HOXB) cluster genes in purified HPCs induced in liquid suspension culture to gradual erythroid or granulopoietic (largely eosinophilic) differentiation and maturation by differential growth factor (GF) stimulus [25].

References