Structure and acetyl-lysine recognition of the bromodomain

Oncogene. 2007 Aug 13;26(37):5521-7. doi: 10.1038/sj.onc.1210618.

Abstract

Histone lysine acetylation is central to epigenetic control of gene transcription. The bromodomain, found in chromatin-associated proteins and histone acetyltranferases, functions as the sole protein module known to bind acetyl-lysine motifs. Recent structural and functional analyses of bromodomains' recognition of lysine-acetylated peptides derived from major acetylation sites in histones and cellular proteins provide new insights into differences in ligand binding selectivity as well as unifying features of histone recognition by the bromodomains. These new findings highlight the functional importance of bromodomain/acetyl-lysine binding as a pivotal mechanism for regulating protein-protein interactions in histone-directed chromatin remodeling and gene transcription. These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Cycle Proteins / chemistry*
  • Histone Acetyltransferases / chemistry*
  • Humans
  • Ligands
  • Lysine / chemistry*
  • Protein Conformation
  • Protein Structure, Tertiary
  • Transcription Factors / chemistry*
  • p300-CBP Transcription Factors

Substances

  • Cell Cycle Proteins
  • Ligands
  • Transcription Factors
  • Histone Acetyltransferases
  • p300-CBP Transcription Factors
  • p300-CBP-associated factor
  • Lysine