Independent dynamic regulation of histone phosphorylation and acetylation during immediate-early gene induction.
Induction of c-fos and c-jun is associated with phosphoacetylation of histone H3 and acetylation of histone H4. Upon induction, a large population of nucleosomes becomes highly acetylated on histones H3 and H4, whereas a much smaller population of comparable nucleosomes at similar positions along the gene becomes phosphoacetylated. Inhibiting histone H3 phosphorylation with kinase inhibitors does not measurably alter the enhanced acetylation of these nucleosomes. Finally, whereas H3 phosphorylation is a MAP kinase-mediated inducible event, we found acetylation to be continuously turning over by the targeted action of HATs and HDACs in the absence of any stimulation or gene transcription. These studies suggest that phosphorylation and acetylation are independently and dynamically regulated at these genes and reveal the complexity of multiple histone modifications at immediate-early gene chromatin.
Thomson
S
S
Nuclear Signalling Laboratory, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, United Kingdom.
Clayton
A L
AL
Mahadevan
L C
LC
D000107:Acetylation / Q000187:drug effects; D000123:Acetyltransferases / Q000037:antagonists & inhibitors; D000818:Animals; D000906:Antibodies / Q000276:immunology; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017781:Genes, Immediate-Early / Q000235:genetics*; D016758:Genes, jun / Q000235:genetics*; D051548:Histone Acetyltransferases; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009707:Nucleosomes / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D029701:Saccharomyces cerevisiae Proteins; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000906:Antibodies; D002843:Chromatin; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D020928:Mitogen-Activated Protein Kinases