title: PRC2 and SWI/SNF Chromatin Remodeling Complexes in Health and Disease.
abstract: The dynamic structure of histones and DNA, also known as chromatin, is regulated by two classes of enzymes: those that mediate covalent modifications on either histone proteins or DNA and those that use the energy generated by ATP hydrolysis to mechanically alter chromatic structure. Both classes of enzymes are often found in large protein complexes. In this review, we describe two such complexes: polycomb repressive complex 2 (PRC2), with the protein methyltransferase EZH2 as its catalytic subunit, and the ATP-dependent chromatin remodeler switch/sucrose non-fermentable (SWI/SNF). EZH2 catalyzes the methylation of lysine 27 on histone H3, a covalent chromatin modification that is associated with repressed heterochromatin. The catalytic activity of SWI/SNF, in contrast, leads to a state of open chromatin associated with active transcription. In this review, we discuss the biochemical properties of both complexes, outline the principles of their regulation, and describe their opposing roles in normal development, which can be perturbed in disease settings such as cancer.
authors.affiliation: Dana-Farber Cancer Institute and Harvard Medical School , 450 Brookline Avenue, Boston, Massachusetts 02215, United States.
authors.forename: Cigall
authors.initials: C
authors.lastname: Kadoch
authors.affiliation: Epizyme Inc. , 400 Technology Square, 4th floor, Cambridge, Massachusetts 02139, United States.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Copeland
authors.affiliation: Epizyme Inc. , 400 Technology Square, 4th floor, Cambridge, Massachusetts 02139, United States.
authors.forename: Heike
authors.initials: H
authors.lastname: Keilhack
mesh_terms: D000818:Animals; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein; D006570:Heterochromatin / Q000378:metabolism / Q000473:pathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D009363:Neoplasm Proteins / Q000378:metabolism* / Q000494:pharmacology*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D004273:DNA, Neoplasm; D006570:Heterochromatin; D006657:Histones; D009363:Neoplasm Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2