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Frontiers in Biology

ISSN 1674-7984

ISSN 1674-7992(Online)

CN 11-5892/Q

Front Biol    2012, Vol. 7 Issue (3) : 202-211    https://doi.org/10.1007/s11515-012-1189-z
REVIEW
ATP-dependent chromatin remodeling complex SWI/SNF in cardiogenesis and cardiac progenitor cell development
Ienglam LEI1,2,3, Mai Har SHAM3, Zhong WANG1,2()
1. Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA; 2. Harvard Stem Cell Institute, 185 Cambridge Street, Boston, MA 02114, USA; 3. Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
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Abstract

The recent identification of cardiac progenitor cells (CPCs) provides a new paradigm for studying and treating heart disease. To realize the full potential of CPCs for therapeutic purposes, it is essential to understand the genetic and epigenetic mechanisms guiding CPC differentiation into cardiomyocytes, smooth muscle, or endothelial cells. ATP-dependent chromatin remodelers mediate one critical epigenetic mechanism. These large multiprotein complexes open up chromatin to modulate transcription factor access to DNA. SWI/SNF, one of the major types of chromatin remodelers, plays a key role in various aspects of development (de la Serna et al., 2006; Wu et al., 2009), including heart development and disease (Lickert et al., 2004; Wang et al., 2004; Huang et al., 2008; Stankunas et al., 2008; Hang et al., 2010). In this review, we describe the specific function of various SWI/SNF components in cardiogenesis and cardiac progenitor cell (CPC) self-renewal and differentiation. We envision that a detailed understanding of the SWI/SNF in heart development and CPC formation and differentiation will generate novel insights into epigenetic mechanisms that govern CPC differentiation and may have significant implications in understanding and treating heart disease.

Keywords ATP-dependent chromatin remodeling      SWI/SNF      cardiogenesis and cardiac progenitor cell     
Corresponding Author(s): WANG Zhong,Email:zhwang@partners.org   
Issue Date: 01 June 2012
 Cite this article:   
Ienglam LEI,Mai Har SHAM,Zhong WANG. ATP-dependent chromatin remodeling complex SWI/SNF in cardiogenesis and cardiac progenitor cell development[J]. Front Biol, 2012, 7(3): 202-211.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-012-1189-z
https://academic.hep.com.cn/fib/EN/Y2012/V7/I3/202
Fig.1  Two major forms of ATP-dependent chromatin remodeling. Note that the remodeling can be bidirectional.
Fig.2  A diagram of SWI/SNF complexes. The composition and stoichiometry of SWI/SNF may determine its cell type specific function. In mammalian cells, SWI/SNF can be further divided into two subcomplexes, called BAF and PBAF. BAF250a (Osa1) and BAF250b (Osa2) are uniquely present in BAF, whereas BAF180 and BAF200 are only associated with PBAF. There are also tissue specific subunits (Table 1).
SubunitDevelopmental function
Brg1Brg1 null embryos die at peri-implantation. Brg1 is essential for T cell development and embryonic erythropoiesis. Brg1 is required for differentiation of neurons, lymphocytes, adipocytes and heart.
BAF250BAF250a knockout embryos die at E6.5 and affecting mesodermal lineage. Embryos lacking one copy of BAF250a show haploid insufficiency in heart chamber maturation. BAF250a knockout ES cells show defects in cardiomyocyte differentiation. BAF250b knockout ES cells have spontaneous differentiation.
BAF155BAF155 knockout is embryonic lethal. Heterozygotes show defects in neuron development.
BAF60BAF60c is required for embryonic heart development
BAF53BAF53a is required for the cell cycle exit neuronal progenitor cells. BAF53b promotes dendritic outgrowth.
BAF45BAF45a is sufficient for inducing proliferation in neuronal progenitor cells. BAF45c regulates cardiomyocytes development.
BAF 180BAF180 is required for myocardium development and coronary formation.
Tab.1  Functions of BAF complex subunits during development
Fig.3  Proposed model for BAF250a-, BAF60c-, and Brg1-mediated chromatin remodeling in gene expression during SHF cardiac development. During cardiac development, BAF250a and BAF60c regulate the recruitment of Brg1 to the target genes. Brg1 then remodels the nucleosome structure allowing transcription factors access to regulatory DNA elements and eventually maintain proper expression of specific gene program. TFs: transcript factors.
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