title: Small molecule control of chromatin remodeling.
abstract: Control of cellular transcriptional programs is based on reversible changes in chromatin conformation that affect access of the transcriptional machinery to specific gene promoters. Chromatin conformation is in turn controlled by the concerted effects of reversible, covalent modification of the DNA and histone components of chromatin, along with topographical changes in DNA-histone interactions; all of these chromatin-modifying reactions are catalyzed by specific enzymes and are communicated to the transcriptional machinery by proteins that recognize and bind to unique, covalent modifications at specific chromatin sites (so-called reader proteins). Over the past decade, considerable progress has been made in the discovery of potent and selective small molecule modulators of specific chromatin-modifying proteins. Here we review the progress that has been made toward small molecule control of these mechanisms and the potential clinical applications of such small molecule modulators of chromatin remodeling.
authors.affiliation: Epizyme, Inc., 400 Technology Square, 4th Floor, Cambridge, MA 02139, USA.
authors.forename: Aidan
authors.initials: A
authors.lastname: Finley
authors.affiliation: Epizyme, Inc., 400 Technology Square, 4th Floor, Cambridge, MA 02139, USA. Electronic address: rcopeland@epizyme.com.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Copeland
mesh_terms: D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D056466:Histone Demethylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008745:Methylation; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology
chemical_list: D002843:Chromatin; D004791:Enzyme Inhibitors; D006657:Histones; D054852:Small Molecule Libraries; D056466:Histone Demethylases; D008780:Methyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases