Phosphorylation of serine 10 in histone H3 is functionally linked in vitro and in vivo to Gcn5-mediated acetylation at lysine 14.
Multiple covalent modifications exist in the amino-terminal tails of core histones, but whether a relationship exists between them is unknown. We examined the relationship between serine 10 phosphorylation and lysine 14 acetylation in histone H3 and have found that, in vitro, several HAT enzymes displayed increased activity on H3 peptides bearing phospho-Ser-10. This augmenting effect of Ser-10 phosphorylation on acetylation by yGcn5 was lost by substitution of alanine for arginine 164 [Gcn5(R164A)], a residue close to Ser-10 in the structure of the ternary tGcn5/CoA/histone H3 complex. Gcn5(R164A) had reduced activity in vivo at a subset of Gcn5-dependent promoters, and, strikingly, transcription of this same subset of genes was also impaired by substitution of serine 10 to alanine in the histone H3 tail. These observations suggest that transcriptional regulation occurs by multiple mechanistically linked covalent modifications of histones.
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Molecular Genetics Program, Wistar Institute, Philadelphia, Pennsylvania 19024, USA.
Trievel
R C
RC
Rojas
J R
JR
Duggan
L
L
Hsu
J Y
JY
Allis
C D
CD
Marmorstein
R
R
Berger
S L
SL
D000107:Acetylation; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051548:Histone Acetyltransferases; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D046911:Macromolecular Substances; D008954:Models, Biological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine / Q000378:metabolism*; D013379:Substrate Specificity; D015533:Transcriptional Activation / Q000235:genetics; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D001120:Arginine; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D008239:Lysine; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010768:Phosphoserine; D011494:Protein Kinases; D011994:Recombinant Proteins; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor