title: Phosphorylation of histone H3 is functionally linked to retinoic acid receptor beta promoter activation.
abstract: Ligand-dependent transcriptional activation of retinoic acid receptors (RARs) is a multistep process culminating in the formation of a multimeric co-activator complex on regulated promoters. Several co-activator complexes harbor an acetyl transferase activity, which is required for retinoid-induced transcription of reporter genes. Using murine P19 embryonal carcinoma cells, we examined the relationship between histone post-translational modifications and activation of the endogenous RARbeta2 promoter, which is under the control of a canonical retinoic acid response element and rapidly induced upon retinoid treatment. While histones H3 and H4 were constitutively acetylated at this promoter, retinoid agonists induced a rapid phosphorylation at Ser10 of histone H3. A retinoid antagonist, whose activity was independent of co-repressor binding to RAR, could oppose this agonist-induced H3 phosphorylation. Since such post-translational modifications were not observed at several other promoters, we conclude that histone H3 phosphorylation may be a molecular signature of the activated, retinoid-controlled mRARbeta2 gene promoter.
authors.affiliation: Laboratory of Molecular Growth Regulation, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA. p.lefebvre@lille.inserm.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Lefebvre
authors.forename: Keiko
authors.initials: K
authors.lastname: Ozato
authors.forename: Philippe
authors.initials: P
authors.lastname: Lefebvre
mesh_terms: D000818:Animals; D006657:Histones / Q000378:metabolism*; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D006656:Protamine Kinase / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D014212:Tretinoin / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D006657:Histones; D018168:Receptors, Retinoic Acid; C082925:retinoic acid receptor beta; D014212:Tretinoin; D006656:Protamine Kinase