The bromodomain mediates transcriptional intermediary factor 1alpha -nucleosome interactions

J Biol Chem. 2002 Dec 27;277(52):50318-25. doi: 10.1074/jbc.M203759200. Epub 2002 Oct 15.

Abstract

Nuclear histone acetyltransferases, DNA-dependent ATPases, and transcriptional intermediary factors (TIFs) all harbor a distinct structural module known as the bromodomain (BrD). Although the BrD can interact with histones H3 and H4 and their acetylated N-terminal tails in vitro, its function in a chromosomal environment remains elusive. We used the nuclear receptor coregulator TIF1alpha, a protein kinase that associates tightly with euchromatin, to analyze the properties of the BrD in a nucleosomal environment in vitro. Here, we report that TIF1alpha-chromatin association is direct and involves DNA and nucleosome interactions mediated by the BrD. Mutation of the BrD signature peptide, PMDL, abolishes DNA binding and disrupts BrD-nucleosome interactions. Based on our results, we propose that the BrD plays a critical role in vivo by directing transregulators to their cognate location on nucleosomal DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Chromatin / metabolism
  • Cloning, Molecular
  • Drosophila / embryology
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Histones / metabolism
  • Molecular Sequence Data
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Nucleosomes / metabolism*
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism*
  • Protein Kinases / chemistry
  • Protein Kinases / genetics
  • Protein Kinases / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*

Substances

  • Chromatin
  • Drosophila Proteins
  • Histones
  • Nuclear Proteins
  • Nucleosomes
  • Peptide Fragments
  • Recombinant Proteins
  • Transcription Factors
  • transcriptional intermediary factor 1
  • Protein Kinases

Associated data

  • GENBANK/AY155467
  • GENBANK/AY155468