Synergistic coupling of histone H3 phosphorylation and acetylation in response to epidermal growth factor stimulation.
Histone acetylation and phosphorylation have separately been suggested to affect chromatin structure and gene expression. Here we report that these two modifications are synergistic. Stimulation of mammalian cells by epidermal growth factor (EGF) results in rapid and sequential phosphorylation and acetylation of H3, and these dimodified H3 molecules are preferentially associated with the EGF-activated c-fos promoter in a MAP kinase-dependent manner. In addition, the prototypical histone acetyltransferase Gcn5 displays an up to 10-fold preference for phosphorylated (Ser-10) H3 over nonphosphorylated H3 as substrate in vitro, suggesting that H3 phosphorylation can affect the efficiency of subsequent acetylation reactions. Together, these results illustrate how the addition of multiple histone modifications may be coupled during the process of gene expression.
Cheung
P
P
Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville 22908, USA.
Tanner
K G
KG
Cheung
W L
WL
Sassone-Corsi
P
P
Denu
J M
JM
Allis
C D
CD
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D016762:Genes, fos / Q000235:genetics; D051548:Histone Acetyltransferases; D006657:Histones / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D007700:Kinetics; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000235:genetics; D011494:Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D013379:Substrate Specificity; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D000906:Antibodies; D002843:Chromatin; D004268:DNA-Binding Proteins; D004815:Epidermal Growth Factor; D005656:Fungal Proteins; D051548:Histone Acetyltransferases; D006657:Histones; D020928:Mitogen-Activated Protein Kinases; D011494:Protein Kinases; D029701:Saccharomyces cerevisiae Proteins; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor