MAP kinase-mediated phosphorylation of distinct pools of histone H3 at S10 or S28 via mitogen- and stress-activated kinase 1/2

• DOI: 10.1242/jcs.02373
• Publication Date: 2005-05-04T02:28:36Z
• Authors: Mark H. Dyson; Stuart Thomson; Masaki Inagaki; Hidemasa Goto; Simon J. Arthur; Karl Nightingale; Francisco J. Iborra; Louis C. Mahadevan
• Keywords: 570; 610; Gene induction; Hydroxamic Acids; Transfection; name=Cell Biology; Cell Line; Histones; Mice; 03 medical and health sciences; Mitogen-Activated Protein Kinase 11; Serine; MSK; Animals; Mitogen-Activated Protein Kinase 8; Phosphorylation; Interphase; Cell Nucleus; 0303 health sciences; Epidermal Growth Factor; Acetylation; Chromatin; Histone H3 phosphorylation; MAP kinases; Tetradecanoylphorbol Acetate; /dk/atira/pure/subjectarea/asjc/1300/1307; Anisomycin

ERK and p38 MAP kinases, acting through the downstream mitogen- stress-activated kinase 1/2 (MSK1/2), elicit histone H3 phosphorylation on a subfraction of nucleosomes – including those at Fos Jun concomitant with gene induction. S10 S28 tail have both been shown to be phospho-acceptors in vivo. Both phospho-epitopes appear similar time-courses occur tails that are highly sensitive TSA-induced hyperacetylation, similarities which might suggest MSK1/2 phosphorylates sites same tails. Indeed, recombinant octamers vitro, MSK1 efficiently tail. However, sequential immunoprecipitation studies show antibodies against phosphorylated S10-H3 recover virtually all this epitope without depletion S28-H3, vice versa, indicating two not located Confocal immunocytochemistry confirms clear physical separation intact mouse nucleus. Finally, we used transfection-based experiments test models explain such differential targeting. Overexpression delocalisation does result breakdown targeting vivo despite fact ectopic is fully activated by external stimuli. These reveal remarkable level distinct within chromatin interphase Possible for exquisite discussed.