The Homeodomain Protein Barx2 Promotes Myogenic Differentiation and Is Regulated by Myogenic Regulatory Factors

Meech, Robyn; Makarenkova, Helen P.; Edelman, David B.; Jones, Frederick S.

doi:10.1074/jbc.m207617200

Cited by 23 publications

(38 citation statements)

References 53 publications

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“…These stimuli trigger signaling cascades that culminate in the activation of transcription factors such as AP1, fos, jun and ETS that bind directly to MMP gene promoters (Chakraborti et al, 2003). BARX2 might interact with such factors, as it is known to bind to leucine-zipper proteins (Meech et al, 2003) and SRF (Herring et al, 2001). Estrogen also influenced BARX2-mediated regulation of TIMP1 and TIMP3, consistent with previous observations that steroid hormones regulate TIMPs (Nothnick et al, 2004).…”

Section: Discussionsupporting

confidence: 87%

“…BARX2 might promote serum-dependent migration by any of these mechanisms. For example, BARX2 influences the cytoskeleton (Meech et al, 2003) and interacts with the serum response factor (SRF) (Herring et al, 2001), which controls actin-directed cell spreading (Schratt et al, 2002). BARX2 also increases transcription of MMP9, which is known to promote invasion of cancer cells via matrix degradation (Vu et al, 1998;Balduyck et al, 2000;Zhao et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…We previously characterized a homeodomain protein Barx2 that is expressed in several tissues during mouse development, including cartilage, muscle and branching epithelial structures such as the mammary and lacrimal glands (Jones et al, 1997;Herring et al, 2001;Meech et al, 2003;and unpublished observations). Barx2 controls processes involving cell adhesion and cytoskeletal remodeling, including myogenesis and chondrogenesis (Meech et al, 2003(Meech et al, , 2005.…”

Section: Introductionmentioning

confidence: 97%

“…Barx2 controls processes involving cell adhesion and cytoskeletal remodeling, including myogenesis and chondrogenesis (Meech et al, 2003(Meech et al, , 2005. Human BARX2 has been described as a potential tumor suppressor gene in ovarian cancer, where its loss correlates with invasiveness, and ectopic expression inhibits invasion (Sellar et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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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: 87%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Murine Barx2 is expressed in several mesenchymal and epithelial tissues during development including cartilage, skeletal and smooth muscle, the central nervous system, and branching epithelial structures, such as the mammary, lacrimal, and salivary glands (6,9,10). 2,3 Our recent studies indicate that Barx2 influences cellular processes that control cell adhesion and remodeling of the actin cytoskeleton seen in myoblast fusion (10), and chondrogenesis.…”

mentioning

confidence: 99%

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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The differentiation and morphogenesis of craniofacial muscles

Noden

Francis‐West

2006

Developmental Dynamics

355

358

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Unraveling the complex tissue interactions necessary to generate the structural and functional diversity present among craniofacial muscles is challenging. These muscles initiate their development within a mesenchymal population bounded by the brain, pharyngeal endoderm, surface ectoderm, and neural crest cells. This set of spatial relations, and in particular the segmental properties of these adjacent tissues, are unique to the head. Additionally, the lack of early epithelialization in head mesoderm necessitates strategies for generating discrete myogenic foci that may differ from those operating in the trunk. Molecular data indeed indicate dissimilar methods of regulation, yet transplantation studies suggest that some head and trunk myogenic populations are interchangeable. The first goal of this review is to present key features of these diversities, identifying and comparing tissue and molecular interactions regulating myogenesis in the head and trunk. Our second focus is on the diverse morphogenetic movements exhibited by craniofacial muscles. Precursors of tongue muscles partly mimic migrations of appendicular myoblasts, whereas myoblasts destined to form extraocular muscles condense within paraxial mesoderm, then as large cohorts they cross the mesoderm:neural crest interface en route to periocular regions. Branchial muscle precursors exhibit yet another strategy, establishing contacts with neural crest populations before branchial arch formation and maintaining these relations through subsequent stages of morphogenesis. With many of the prerequisite stepping-stones in our knowledge of craniofacial myogenesis now in place, discovering the cellular and molecular interactions necessary to initiate and sustain the differentiation and morphogenesis of these neglected craniofacial muscles is now an attainable goal.

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The Homeodomain Protein Barx2 Promotes Myogenic Differentiation and Is Regulated by Myogenic Regulatory Factors

Cited by 23 publications

References 53 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

The differentiation and morphogenesis of craniofacial muscles

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