SWI/SNF Protein Component BAF250a Regulates Cardiac Progenitor Cell Differentiation by Modulating Chromatin Accessibility during Second Heart Field Development

Lei, Ienglam; Gao, Xiaolin; Sham, Mai Har; Wang, Zhong

doi:10.1074/jbc.m112.365080

Cited by 67 publications

(72 citation statements)

References 36 publications

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“…1L). These heart defects bear a striking resemblance to those observed in heterozygous Arid1a-null embryos and in embryos completely lacking ARID1a in second heart field (SHF) derivatives (via Mef2c-AHF-Cre), which further supports a role for ARID1a-containing BAF-A complexes in cardiac progenitor differentiation (23,49). In spite of these similarities, our data suggest that the midgestation lethality observed in Arid1a V1068G/ V1068G embryos is due to the culmination of defects in multiple tissues because SHF-specific loss of ARID1a in the heart results in embryonic lethality at later time points (49).…”

Section: An Enu Mutagenesis Screen In Mouse Es Cells Identifies a Novelsupporting

confidence: 54%

ARID1a-DNA Interactions Are Required for Promoter Occupancy by SWI/SNF

Chandler

Brennan

Schisler

et al. 2013

Molecular and Cellular Biology

103

124

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Every known SWI/SNF chromatin-remodeling complex incorporates an ARID DNA binding domain-containing subunit. Despite being a ubiquitous component of the complex, physiological roles for this domain remain undefined. Here, we show that disruption of ARID1a-DNA binding in mice results in embryonic lethality, with mutant embryos manifesting prominent defects in the heart and extraembryonic vasculature. The DNA binding-defective mutant ARID1a subunit is stably expressed and capable of assembling into a SWI/SNF complex with core catalytic properties, but nucleosome substrate binding and promoter occupancy by ARID1a-containing SWI/SNF complexes (BAF-A) are impaired. Depletion of ARID domain-dependent, BAF-A associations at THROMBOSPONDIN 1 (THBS1) led to the concomitant upregulation of this SWI/SNF target gene. Using a THBS1 promoter-reporter gene, we further show that BAF-A directly regulates THBS1 promoter activity in an ARID domain-dependent manner. Our data not only demonstrate that ARID1a-DNA interactions are physiologically relevant in higher eukaryotes but also indicate that these interactions facilitate SWI/SNF binding to target sites in vivo. These findings support the model wherein cooperative interactions among intrinsic subunit-chromatin interaction domains and sequence-specific transcription factors drive SWI/SNF recruitment.

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Section: An Enu Mutagenesis Screen In Mouse Es Cells Identifies a Novelsupporting

confidence: 54%

ARID1a-DNA Interactions Are Required for Promoter Occupancy by SWI/SNF

Chandler

Brennan

Schisler

et al. 2013

Molecular and Cellular Biology

103

124

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“…RNAi of BAF60c in mice leads to severe cardiac defects, including single ventricle, shortened outflow tract, and hypotrabeculation (Lickert et al 2004), and deletion of BAF60c in zebrafish affects cardiac progenitor formation and migration to the developing heart tube . Similarly, BAF250a deletion suggested involvement in the formation of cardiac progenitor cells (Lei et al 2012). Deletion of BAF180 causes hypoplastic ventricle development reminiscent of defects in retinoic acid signaling, consistent with its role in the transcriptional response to ligands and nuclear receptors (Wang et al 2004).…”

Section: Combinatorial Swi/snf Code For Muscle Determinationmentioning

confidence: 68%

BAF60 A, B, and Cs of muscle determination and renewal

Puri

Mercola

2012

Genes Dev.

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Developmental biologists have defined many of the diffusible and transcription factors that control muscle differentiation, yet we still have only rudimentary knowledge of the mechanisms that dictate whether a myogenic progenitor cell forms muscle versus alternate lineages, including those that can be pathological in a state of disease or degeneration. Clues about the molecular basis for lineage determination in muscle progenitors are only now emerging from studies of chromatin modifications that avail myogenic genes for transcription, together with analysis of the composition and activities of the chromatin-modifying complexes themselves. Here we review recent progress on muscle determination and explore a unifying theme that environmental cues from the stem or progenitor niche control the selection of specific subunit variants of the switch/sucrose nonfermentable (SWI/SNF) chromatin-modifying complex, creating a combinatorial code that dictates whether cells adopt myogenic versus nonmyogenic cell fates. A key component of the code appears to be the mutually exclusive usage of the a, b, and c variants of the 60-kD structural subunit BAF60 (BRG1/BRM-associated factor 60), of which BAF60c is essential to activate both skeletal and cardiac muscle programs. Since chromatin remodeling governs myogenic fate, the combinatorial assembly of the SWI/SNF complex might be targeted to develop drugs aimed at the therapeutic reduction of compensatory fibrosis and fatty deposition in chronic muscular disorders.

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“…3H,I), suggesting that Cer1 induces Baf60c. Baf250a, Baf250b, and Baf180, previously implicated in myocardial development (Wang et al 2004;Lei et al 2012), were unaffected (Fig. 4B).…”

Section: Nodal and Bmp Inhibition Induce The Swi/snf Component Baf60cmentioning

confidence: 84%

Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment

et al. 2013

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A critical but molecularly uncharacterized step in heart formation and regeneration is the process that commits progenitor cells to differentiate into cardiomyocytes. Here, we show that the endoderm-derived dual Nodal/bone morphogenetic protein (BMP) antagonist Cerberus-1 (Cer1) in embryonic stem cell cultures orchestrates two signaling pathways that direct the SWI/SNF chromatin remodeling complex to cardiomyogenic loci in multipotent (KDR/Flk1 + ) progenitors, activating lineage-specific transcription. Transient inhibition of Nodal by Cer1 induces Brahma-associated factor 60c (Baf60c), one of three Baf60 variants (a, b, and c) that are mutually exclusively assembled into SWI/SNF. Blocking Nodal and BMP also induces lineage-specific transcription factors Gata4 and Tbx5, which interact with Baf60c. siRNA to Cer1, Baf60c, or the catalytic SWI/SNF subunit Brg1 prevented the developmental opening of chromatin surrounding the Nkx2.5 early cardiac enhancer and cardiomyocyte differentiation. Overexpression of Baf60c fully rescued these deficits, positioning Baf60c and SWI/ SNF function downstream from Cer1. Thus, antagonism of Nodal and BMP coordinates induction of the myogenic Baf60c variant and interacting transcription factors to program the developmental opening of cardiomyocytespecific loci in chromatin. This is the first demonstration that cues from the progenitor cell environment direct the subunit variant composition of SWI/SNF to remodel the transcriptional landscape for lineage-specific differentiation.

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SWI/SNF Protein Component BAF250a Regulates Cardiac Progenitor Cell Differentiation by Modulating Chromatin Accessibility during Second Heart Field Development

Cited by 67 publications

References 36 publications

ARID1a-DNA Interactions Are Required for Promoter Occupancy by SWI/SNF

ARID1a-DNA Interactions Are Required for Promoter Occupancy by SWI/SNF

BAF60 A, B, and Cs of muscle determination and renewal

Coordinate Nodal and BMP inhibition directs Baf60c-dependent cardiomyocyte commitment

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