The bromodomain: from epigenome reader to druggable target

R Sanchez, J Meslamani, MM Zhou - Biochimica et Biophysica Acta (BBA) …, 2014 - Elsevier
Biochimica et Biophysica Acta (BBA)-Gene Regulatory Mechanisms, 2014Elsevier
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 …
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.
Elsevier