title: Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing.
abstract: Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activator. Targeting of this H3 kinase to the endogenous c-fos promoter is sufficient to activate its expression without the need of upstream signaling. Moreover, targeting MSK1 to the α-globin promoter induces H3 S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Importantly, we discovered a mechanism whereby H3 S28 phosphorylation not only displaces binding of the polycomb-repressive complexes, but it also induces a methyl-acetylation switch of the adjacent K27 residue. Our findings show that signal transduction activation can directly regulate polycomb silencing through a specific histone code-mediated mechanism.
authors.affiliation: Ontario Cancer Institute, Toronto, ON, Canada M5G 2M9.
authors.forename: Priscilla Nga Ieng
authors.initials: PN
authors.lastname: Lau
authors.forename: Peter
authors.initials: P
authors.lastname: Cheung
mesh_terms: D000107:Acetylation; D000818:Animals; D002460:Cell Line; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation / Q000502:physiology*; D020868:Gene Silencing; D016762:Genes, fos / Q000235:genetics; D006657:Histones / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D008156:Luciferases; D051379:Mice; D010766:Phosphorylation; D063146:Polycomb-Group Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D055542:alpha-Globins / Q000235:genetics
chemical_list: D006657:Histones; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D055542:alpha-Globins; D008156:Luciferases; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C116919:mitogen and stress-activated protein kinase 1