Acetylation of novel sites in the nucleosomal binding domain of chromosomal protein HMG-14 by p300 alters its interaction with nucleosomes.
The reversible acetylation of histones is associated with structural alterations in the chromatin fiber that affect various DNA-related activities. Here we show that the histone acetyltransferase p300 specifically acetylates HMG-14, a nonhistone structural protein that binds to nucleosomes and reduces the compactness of the chromatin fiber. We identify 7 major acetylation sites, 6 of which are novel and have not been known to be acetylated in either HMG-14 or the closely related HMG-17 protein. All the acetylation sites involve evolutionarily conserved residues: 3 within the HMG-14/-17 nucleosomal binding domain and 4 in or near the bipartite nuclear localization domains of the proteins. In tissue culture cells the acetylation pattern is indicative of a selective process in which a subfraction of HMG-14 is preferentially acetylated. We find that the nucleosomal binding domain is a major target for acetylation in vivo and that the specific acetylation of HMG-14 by p300 weakens its interaction with nucleosome cores. Our results suggest that p300 modulates the interaction of HMG-14 with nucleosomes. Thus, p300 may affect chromatin-related activities not only by modifying histones or transcription factors but also by targeting structural nonhistone proteins.
Bergel
M
M
Protein Section, Division of Basic Science, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA. bergel@helix.nih.gov
Herrera
J E
JE
Thatcher
B J
BJ
Prymakowska-Bosak
M
M
Vassilev
A
A
Nakatani
Y
Y
Martin
B
B
Bustin
M
M
D000107:Acetylation; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000502:physiology; D006367:HeLa Cells; D006609:High Mobility Group Proteins / Q000378:metabolism*; D006801:Humans; D009707:Nucleosomes / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology
D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D009707:Nucleosomes; D015534:Trans-Activators; D014157:Transcription Factors