The bromodomain mediates transcriptional intermediary factor 1alpha -nucleosome interactions.
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.
Remboutsika
Eumorphia
E
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/Université Louis Pasteur, BP 163, F-67404 Illkirch cedex, France. erembou@nimr.mrc.ac.uk
Yamamoto
Ken
K
Harbers
Matthias
M
Schmutz
Marc
M
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002843:Chromatin / Q000378:metabolism; D003001:Cloning, Molecular; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D009707:Nucleosomes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014157:Transcription Factors; C093517:transcriptional intermediary factor 1; D011494:Protein Kinases