title: Mitogen-stimulated phosphorylation of histone H3 is targeted to a small hyperacetylation-sensitive fraction.
abstract: Diverse agents, including growth factors and phorbol esters, induce rapid transcriptional activation of a subset of immediate-early (IE) genes that include the protooncogenes c-fos and c-jun. Among the earliest nuclear signaling events concomitant with IE gene activation is the phosphorylation of nucleosomal histone H3 in its basically charged N-terminal tail. This highly conserved domain is also subject to reversible posttranslational acetylation at specific lysine residues, a process implicated in transcriptional regulation. We show here that H3 phosphorylation associated with G0-G1 transition affects only a small fraction of this histone in the nucleus. Moreover, this fraction is biochemically distinct from bulk H3 in being extremely sensitive to sodium butyrate-induced hyperacetylation. However, acetylation itself does not predispose H3 to phosphorylation, nor does phosphorylation predispose H3 to enhanced acetylation. Further, selectivity is not based on preferential modification of particular histone H3 subtypes. Thus, the mitogen-regulated kinase that phosphorylates histone H3 is restricted to a small subset of nucleosomes that is especially susceptible to hyperacetylation.
authors.affiliation: Nuclear Signalling Laboratory, Randall Institute, King's College London, England.
authors.forename: M J
authors.initials: MJ
authors.lastname: Barratt
authors.forename: C A
authors.initials: CA
authors.lastname: Hazzalin
authors.forename: E
authors.initials: E
authors.lastname: Cano
authors.forename: L C
authors.initials: LC
authors.lastname: Mahadevan
mesh_terms: D000107:Acetylation; D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002453:Cell Cycle; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051379:Mice; D008934:Mitogens / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D015533:Transcriptional Activation
chemical_list: D002087:Butyrates; D006657:Histones; D008934:Mitogens; D010446:Peptide Fragments; D020148:Butyric Acid