Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational…

• EL
  Eli Lilly and Company
• P
  Pfizer
• G
  GlaxoSmithKline
• GC
  Genome Canada
• WT
  Wellcome Trust

  Awards: 095751/Z/11/Z, 1097737
• CR
  Canada Research Chairs
• NS
  Natural Sciences and Engineering Research Council of Canada

  Award: 1097737
• OM
  Ontario Ministry of Research and Innovation