Identification of histone H3 lysine 36 acetylation as a highly conserved histone modification.
Histone lysine acetylation is a major mechanism by which cells regulate the structure and function of chromatin, and new sites of acetylation continue to be discovered. Here we identify and characterize histone H3K36 acetylation (H3K36ac). By mass spectrometric analyses of H3 purified from Tetrahymena thermophila and Saccharomyces cerevisiae (yeast), we find that H3K36 can be acetylated or methylated. Using an antibody specific to H3K36ac, we show that this modification is conserved in mammals. In yeast, genome-wide ChIP-chip experiments show that H3K36ac is localized predominantly to the promoters of RNA polymerase II-transcribed genes, a pattern inversely related to that of H3K36 methylation. The pattern of H3K36ac localization is similar to that of other sites of H3 acetylation, including H3K9ac and H3K14ac. Using histone acetyltransferase complexes purified from yeast, we show that the Gcn5-containing SAGA complex that regulates transcription specifically acetylates H3K36 in vitro. Deletion of GCN5 completely abolishes H3K36ac in vivo. These data expand our knowledge of the genomic targets of Gcn5, show H3K36ac is highly conserved, and raise the intriguing possibility that the transition between H3K36ac and H3K36me acts as an "acetyl/methyl switch" governing chromatin function along transcription units.
Morris
Stephanie A
SA
Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
Rao
Bhargavi
B
Garcia
Benjamin A
BA
Hake
Sandra B
SB
Diaz
Robert L
RL
Shabanowitz
Jeffrey
J
Hunt
Donald F
DF
Allis
C David
CD
Lieb
Jason D
JD
Strahl
Brian D
BD
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D047369:Chromatin Immunoprecipitation; D017124:Conserved Sequence; D051548:Histone Acetyltransferases / Q000502:physiology; D006657:Histones / Q000737:chemistry*; D006801:Humans; D008239:Lysine; D008745:Methylation; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012441:Saccharomyces cerevisiae / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D013768:Tetrahymena / Q000737:chemistry; D000099224:p300-CBP-Associated Factor
D051548:Histone Acetyltransferases; D006657:Histones; D008239:Lysine; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor