Cloning and chromosomal localization of the human BARX2 homeobox protein gene

Krasner, Alan; Wallace, Lalena; Thiagalingam, Arunthathi; Jones, Christopher T.; Lengauer, Christoph; Minahan, Lara; Ma, Yongkang; Kalikin, Linda M.; Feinberg, Andrew P.; Jabs, Ethylin Wang; Tunnacliffe, Alan; Baylin, Stephen B.; Ball, Douglas W.; Nelkin, Barry D.

doi:10.1016/s0378-1119(00)00169-4

Cited by 21 publications

(24 citation statements)

References 30 publications

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“…If BARX2 is an intrinsic regulator of MMP and TIMP genes, it might play a role in developmental patterning of the mammary gland. Consistent with this idea, BARX2 is expressed in normal human mammary gland epithelium (Krasner et al, 2000) and influences lacrimal gland branching morphogenesis (unpublished observations). Moreover, the BARX2 targets MMP9, TIMP1 and TIMP3 variously regulate branching morphogenesis in mammary, kidney and bronchiole tissues (Lelongt et al, 1997;Fata et al, 1999;Gill et al, 2003).…”

Section: Discussionsupporting

confidence: 56%

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

Stevens

Meech

2006

Oncogene

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The estrogen receptor-a gene (ESR1) was previously identified as a direct target of the homeobox transcription factor BARX2 in MCF7 cells. Here, we show that BARX2 and ESR1 proteins bind to different ESR1 gene promoters and regulate the expression of alternatively spliced mRNAs that encode 66 and 46 kDa ESR1 protein isoforms. BARX2 increases the expression of both ESR1 isoforms; however, it has a greater effect on the 46 kDa isoform, leading to an increased ratio between the 46 and 66 kDa proteins. BARX2 also influences estrogen-dependent processes such as anchorage-independent growth and modulates the expression of the estrogen-responsive genes SOX5, RBM15, Dynein and Mortalin. In addition, BARX2 expression promotes cellular invasion and increases the expression of active matrix metalloproteinase-9 (MMP9). BARX2 also increases the expression of the tissue inhibitor of metalloproteinase (TIMP) genes, TIMP1 and TIMP3, in cooperation with estrogen signaling. Overall, these data indicate that BARX2 and ESR1 may coordinately regulate cell growth, survival and invasion pathways that are critical to breast cancer progression.

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Section: Discussionsupporting

confidence: 56%

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

Stevens

Meech

2006

Oncogene

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“…As an example, characterization of the Bx23 and Bx68 fragments using ChIP, computational analysis, EMSA, and promoter assays demonstrated that they contain bona fide BARX2 binding elements that are required for regulation by BARX2 in MCF7 cells. This functional HBS element is similar to the consensus BARX2 binding sequence identified through in vitro selection studies (19) in that it contained a TAAT motif and a poly-T rich region. However, the HBS element derived from Bx23 and Bx68 is longer and contains multiple TAAT motifs, some of which overlap.…”

Section: Discussionmentioning

confidence: 62%

“…In addition, the regular expression search tool RIGHT (18) was used to search the sequences for potential BARX2 binding motifs similar to those identified previously in the mouse Ncam1 and L1cam, and chicken NgCAM genes (3), or to the consensus binding motif identified previously by in vitro selection (19).…”

Section: Methodsmentioning

confidence: 99%

“…Fragments-Like most homeodomain proteins, BARX2 binds to motifs that contain the core sequence, TAAT (3,6,19) however, further requirements for BARX2 binding have not been well defined. Earlier studies showed that BARX2 bound with high affinity to the HBS element from the murine Ncam1 promoter (3).…”

Section: Barx2 Binds Preferentially To Paired Taat Motifs Within Barxmentioning

confidence: 99%

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Identification of Novel Binding Elements and Gene Targets for the Homeodomain Protein BARX2

Stevens

Iacovoni

Edelman

et al. 2004

Journal of Biological Chemistry

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BARX2 is a homeobox transcription factor that influences cellular differentiation in various developmental contexts. To begin to identify the gene targets that mediate its effects, chromatin immunoprecipitation (ChIP) was used to isolate BARX2 binding sites from the human MCF7 breast cancer cell line. Cloning and sequencing of BARX2-ChIP-derived DNA fragments identified 60 potential BARX2 target loci that were proximal to or within introns of genes involved in cytoskeletal organization, cell adhesion, growth factor signaling, transcriptional regulation, and RNA metabolism. The sequences of over half of the fragments showed homology with the mouse genome, and several sequences could be mapped to orthologous human and mouse genes. Binding of BARX2 to 21 genomic loci examined was confirmed quantitatively by replicate ChIP assays. A combination of sequence analysis and electrophoretic mobility shift assays revealed homeodomain binding sites within several fragments that bind to BARX2 in vitro. The majority of BARX2 binding fragments tested (14/19), also affected transcription in luciferase reporter gene assays. Mutation analyses of three fragments showed that their transcriptional activities required the HBS, and suggested that BARX2 regulates gene expression by binding to DNA elements containing paired TAAT motifs that are separated by a poly(T) sequence. Inhibition of BARX2 expression in MCF7 cells led to reduced expression of eight genes associated with BARX2 binding sites, indicating that BARX2 directly regulates their expression. The data suggest that BARX2 can coordinate the expression of a network of genes that influence the growth of MCF7 cells.

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“…However, this region is not in the deleted region of Patient 1, who also displays typical craniofacial abnormalities. Furthermore, Krasner et al 18 reported no mutation in the BARX2 gene in nine patients with isolated tigonocephaly. Therefore, it can be presumed that there may be other genes or regions that account for the craniofacial abnormalities in individuals with JBS.…”

Section: Craniofacial Abnormalitiesmentioning

confidence: 99%

Diagnosis and fine mapping of a deletion in distal 11q in two Chinese patients with developmental delay

Wang

et al. 2010

J Hum Genet

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Cloning and chromosomal localization of the human BARX2 homeobox protein gene

Cited by 21 publications

References 30 publications

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

BARX2 and estrogen receptor-α (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion

Identification of Novel Binding Elements and Gene Targets for the Homeodomain Protein BARX2

Diagnosis and fine mapping of a deletion in distal 11q in two Chinese patients with developmental delay

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