Specific acetylation of chromosomal protein HMG-17 by PCAF alters its interaction with nucleosomes.
Nonhistone chromosomal proteins HMG-14 and HMG-17 are closely related nucleosomal binding proteins that unfold the higher-order chromatin structure, thereby enhancing the transcription and replication potential of chromatin. Here we report that PCAF, a transcription coactivator with intrinsic histone acetyltransferase activity, specifically acetylates HMG-17 but not HMG-14. Using mass spectrum sequence analysis, we identified the lysine at position 2 as the predominant site acetylated by PCAF. Lysine 2 is a prominent acetylation site in vivo, suggesting that this PCAF-mediated acetylation is physiologically relevant. Experiments with HMG-17 deletion mutants and competition studies with various protein fragments indicate that the specific acetylation of HMG-17 is not determined solely by the primary sequence near the acetylation site. By equilibrium dialysis we demonstrated that acetylation reduces the affinity of HMG-17 to nucleosome cores. In addition, we found that the binding of HMG-14 and HMG-17 to nucleosome cores inhibits the PCAF-mediated acetylation of histone H3. Thus, the presence of HMG-14 and HMG-17 affects the ability of PCAF to acetylate chromatin, while the acetylation of HMG-17 reduces its binding affinity to chromatin. Conceivably, in HMG-17-containing chromatin, acetylation of HMG-17 precedes the acetylation of histones.
Herrera
J E
JE
Protein Section, Laboratory of Molecular Carcinogenesis, Division of Basic Sciences, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA. Herr@helix.nih.gov
Sakaguchi
K
K
Bergel
M
M
Trieschmann
L
L
Nakatani
Y
Y
Bustin
M
M
D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D002843:Chromatin / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000378:metabolism*; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D013058:Mass Spectrometry; D009707:Nucleosomes / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D006609:High Mobility Group Proteins; D006657:Histones; D009707:Nucleosomes; D010446:Peptide Fragments; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D008239:Lysine