title: Epigenetic Control of Smooth Muscle Cell Identity and Lineage Memory.
abstract: Vascular smooth muscle cells (SMCs), like all cells, acquire a cell-specific epigenetic signature during development that includes acquisition of a unique repertoire of histone and DNA modifications. These changes are postulated to induce an open chromatin state (referred to as euchromatin) on the repertoire of genes that are expressed in differentiated SMC, including SMC-selective marker genes like Acta2 and Myh11, as well as housekeeping genes expressed by most cell types. In contrast, genes that are silenced in differentiated SMC acquire modifications associated with a closed chromatin state (ie, heterochromatin) and transcriptional silencing. Herein, we review mechanisms that regulate epigenetic control of the differentiated state of SMC. In addition, we identify some of the major limitations in the field and future challenges, including development of innovative new tools and approaches, for performing single-cell epigenetic assays and locus-selective editing of the epigenome that will allow direct studies of the functional role of specific epigenetic controls during development, injury repair, and disease, including major cardiovascular diseases, such as atherosclerosis, hypertension, and microvascular disease, associated with diabetes mellitus.
authors.affiliation: From the Department of Molecular Physiology and Biological Physics (D.G., G.K.O.), and Robert M. Berne Cardiovascular Research Center (P.S.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Delphine
authors.initials: D
authors.lastname: Gomez
authors.affiliation: From the Department of Molecular Physiology and Biological Physics (D.G., G.K.O.), and Robert M. Berne Cardiovascular Research Center (P.S.), University of Virginia School of Medicine, Charlottesville.
authors.forename: Pamela
authors.initials: P
authors.lastname: Swiatlowska
authors.affiliation: From the Department of Molecular Physiology and Biological Physics (D.G., G.K.O.), and Robert M. Berne Cardiovascular Research Center (P.S.), University of Virginia School of Medicine, Charlottesville. gko@virginia.edu.
authors.forename: Gary K
authors.initials: GK
authors.lastname: Owens
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000187:drug effects*; D042002:Chromatin Assembly and Disassembly; D053595:Embryonic Stem Cells / Q000378:metabolism* / Q000473:pathology; D044127:Epigenesis, Genetic; D057890:Epigenomics / Q000379:methods; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D006801:Humans; D024510:Muscle Development / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010641:Phenotype
chemical_list: D005819:Genetic Markers
keywords: atherosclerosis; cardiovascular diseases; differentiation; embryonic stem cells; histone modifications; vascular injury; vascular smooth muscle cells