The role of human bromodomains in chromatin biology and gene transcription

Abstract

The acetylation of histone lysine is central to providing the dynamic regulation of chromatin-based gene transcription. The bromodomain (BRD), which is the conserved structural module in chromatin-associated proteins and histone acetyltranferases, is the sole protein domain known to recognize acetyl-lysine residues on proteins. Structural analyses of the recognition of lysine-acetylated peptides derived from histones and cellular proteins by BRDs have provided new insights into the differences between and unifying features of the selectivity that BRDs exhibit in binding biological ligands. Recent research has highlighted the importance of BRD/acetyl-lysine binding in orchestrating molecular interactions in chromatin biology and regulating gene transcription. These studies suggest that modulating BRD/acetyl-lysine interactions with small molecules may provide new opportunities for the control of gene expression in human health and disease.

Figure 1. Structural basis of acetyl-lysine recognition by the bromodomain

(A) The 3-D structure of the CREB binding protein (CBP) bromodomain (BRD) bound to a H4K20ac peptide (PDB code: 2RNY); and (B) the acetyl-lysine binding site, showing the key interactions between the CBP BRD and a H4K20ac peptide. The peptide is yellow and the side chains of the protein residues are color-coded by atom type.