title: SWI/SNF chromatin-remodeling complexes in cardiovascular development and disease.
abstract: Our understanding of congenital heart defects has been recently advanced by whole exome sequencing projects, which have identified de novo mutations in many genes encoding epigenetic regulators. Notably, multiple subunits of switching defective/sucrose non-fermenting (SWI/SNF) chromatin-remodeling complexes have been identified as strong candidates underlying these defects because they physically and functionally interact with cardiogenic transcription factors critical to cardiac development, such as TBX5, GATA-4, and NKX2-5. While these studies indicate a critical role of SWI/SNF complexes in cardiac development and congenital heart disease, many exciting new discoveries have identified their critical role in the adult heart in both physiological and pathological conditions involving multiple cell types in the heart, including cardiomyocytes, vascular endothelial cells, pericytes, and neural crest cells. This review summarizes the role of SWI/SNF chromatin-remodeling complexes in cardiac development, congenital heart disease, cardiac hypertrophy, and vascular endothelial cell survival. Although the clinical relevance of SWI/SNF mutations has traditionally been focused primarily on their role in tumor suppression, these recent studies illustrate their critical role in the heart whereby they regulate cell proliferation, differentiation, and apoptosis of cardiac derived cell lines.
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA.
authors.forename: Ariana
authors.initials: A
authors.lastname: Bevilacqua
authors.affiliation: Department of Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, NC, USA; McAllister Heart Institute, University of North Carolina, Chapel Hill, NC, USA. Electronic address: monte_willis@med.unc.edu.
authors.forename: Monte S
authors.initials: MS
authors.lastname: Willis
authors.affiliation: Department of Genetics, University of North Carolina, Chapel Hill, Chapel Hill, NC, USA. Electronic address: Scott_Bultman@med.unc.edu.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Bultman
mesh_terms: D000818:Animals; D017209:Apoptosis; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002319:Cardiovascular System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D010641:Phenotype; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors
keywords: BAF250a; BRG1; BRM; Cardiovascular; Epigenetics; SWI/SNF