title: The bromodomain: from epigenome reader to druggable target.
abstract: Lysine acetylation is a fundamental post-translational modification that plays an important role in the control of gene transcription in chromatin in an ordered fashion. The bromodomain, the conserved structural module present in transcription-associated proteins, functions exclusively to recognize acetyl-lysine on histones and non-histone proteins. The structural analyses of bromodomains' recognition of lysine-acetylated peptides derived from histones and cellular proteins provide detailed insights into the differences and unifying features of biological ligand binding selectivity by the bromodomains. Newly developed small-molecule inhibitors targeting bromodomain proteins further highlight the functional importance of bromodomain/acetyl-lysine binding as a key mechanism in orchestrating molecular interactions and regulation in chromatin biology and gene transcription. These new studies argue that modulating bromodomain/acetyl-lysine interactions with small-molecule chemicals offer new opportunities to control gene expression in a wide array of human diseases including cancer and inflammation. This article is part of a Special Issue entitled: Molecular mechanisms of histone modification function.
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sanchez
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Jamel
authors.initials: J
authors.lastname: Meslamani
authors.affiliation: Department of Structural and Chemical Biology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Zhou
mesh_terms: D000107:Acetylation; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D015658:HIV Infections / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000821:virology; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones; D054852:Small Molecule Libraries; D014157:Transcription Factors; D008239:Lysine
keywords: Bromodomain; Gene transcription; Small molecule inhibitors