title: cAMP/phorbol ester response element is involved in transcriptional regulation of the human replacement histone gene H3.3B.
abstract: The human histone H3.3B gene belongs to the group of replacement histone genes, which are up-regulated during differentiation of cells. Here we provide evidence that a cAMP response element/PMA response element (CRE/TRE) located in the proximal promoter contributes to the expression of the H3.3B gene. (1) Band shift and supershift analysis demonstrated the binding of AP-1 and transcription factors of the CRE-binding protein/activating-transcription-factor family to the H3.3B CRE/TRE. (2) Treatment of HeLa cells with PMA led to a 4-fold increase in H3. 3B mRNA levels within 2 h, whereas transcription of the cell cycle-dependent H3 histone genes remained constant. In contrast with PMA, cAMP did not affect H3.3B transcription. (3) PMA treatment of cells transiently transfected with H3.3B promoter constructs linked to a luciferase gene caused a 4-5-fold increase in reporter gene activity, whereas mutation of the CRE/TRE element abolished the PMA response. These results demonstrate that activation of the protein kinase C pathway by PMA results in an early up-regulation of H3.3B gene expression via the CRE/TRE element. Furthermore treatment with PMA apparently leads to differential induction of H3 histone subtype genes and this in turn can result in a remodelling of chromatin structure of cells before or during differentiation processes.
authors.affiliation: Institut für Biochemie und Molekulare Zellbiologie, Universität Göttingen, Federal Republic of Germany.
authors.forename: O
authors.initials: O
authors.lastname: Witt
authors.forename: W
authors.initials: W
authors.lastname: Albig
authors.forename: D
authors.initials: D
authors.lastname: Doenecke
mesh_terms: D051696:Activating Transcription Factors; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism; D000242:Cyclic AMP / Q000235:genetics* / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006367:HeLa Cells; D006657:Histones / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D011485:Protein Binding / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D051696:Activating Transcription Factors; D001798:Blood Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D006657:Histones; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D000242:Cyclic AMP; D013755:Tetradecanoylphorbol Acetate