PMID- 17707923 OWN - NLM STAT- MEDLINE DCOM- 20071127 LR - 20181113 IS - 0006-3002 (Print) IS - 0006-3002 (Linking) VI - 1769 IP - 9-10 DP - 2007 Sep-Oct TI - HDAC1 bound to the Cyp1a1 promoter blocks histone acetylation associated with Ah receptor-mediated trans-activation. PG - 569-78 AB - Metabolic bioactivation of polycyclic aromatic hydrocarbons, such as the environmental procarcinogen benzo[a]pyrene, is catalyzed by a cytochrome P450 monooxygenase encoded by the substrate-inducible Cyp1a1 gene. Cyp1a1 induction requires trans-activation by the heterodimeric transcriptional complex formed by the liganded Ah receptor (AHR) and its partner, ARNT. Previously, we showed that constitutively bound HDAC1 dissociates from Cyp1a1 promoter chromatin after ligand-mediated induction, concomitantly with the recruitment of AHR/ARNT complexes and p300. Here, we investigated the hypothesis that HDAC1 binding maintains the Cyp1a1 gene in a silenced state in uninduced cells. We find that Cyp1a1 induction by the AHR/ARNT is associated with modification of specific chromatin marks, including hyperacetylation of histone H3K14 and H4K16, trimethylation of histone H3K4, and phosphorylation of H3S10. HDAC1 and DNMT1 form complexes on the Cyp1a1 promoter of uninduced cells but HDAC1 inhibition alone is not sufficient to induce Cyp1a1 expression, although it allows for the hyperacetylation of H3K14 and H4K16 to levels similar to those found in B[a]P-induced cells. These results show that by blocking the modification of histone marks, HDAC1 plays a central role in Cyp1a1 expression and that its removal is a necessary but not sufficient condition for Cyp1a1 induction, underscoring the requirement for a concerted series of chromatin-remodeling events to complete the initial steps of gene trans-activation by the Ah receptor. FAU - Schnekenburger, Michael AU - Schnekenburger M AD - Center for Environmental Genetics and Department of Environmental Health, University of Cincinnati Medical Center, P.O. Box 670056, Cincinnati, Ohio 45267-0056, USA. FAU - Peng, Li AU - Peng L FAU - Puga, Alvaro AU - Puga A LA - eng GR - R01 ES10807/ES/NIEHS NIH HHS/United States GR - R01 ES010807/ES/NIEHS NIH HHS/United States GR - R01 ES006273/ES/NIEHS NIH HHS/United States GR - P42 ES04908/ES/NIEHS NIH HHS/United States GR - P30 ES006096-14/ES/NIEHS NIH HHS/United States GR - P42 ES004908/ES/NIEHS NIH HHS/United States GR - P30 ES006096/ES/NIEHS NIH HHS/United States GR - P42 ES004908-130012/ES/NIEHS NIH HHS/United States GR - R01 ES06273/ES/NIEHS NIH HHS/United States GR - R01 ES010807-07/ES/NIEHS NIH HHS/United States GR - R01 ES006273-13/ES/NIEHS NIH HHS/United States GR - P30 ES06096/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20070720 PL - Netherlands TA - Biochim Biophys Acta JT - Biochimica et biophysica acta JID - 0217513 RN - 0 (Carrier Proteins) RN - 0 (Fetal Proteins) RN - 0 (Histones) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Receptors, Aryl Hydrocarbon) RN - 0 (TACC3 protein, mouse) RN - 3417WMA06D (Benzo(a)pyrene) RN - EC 1.14.14.1 (Cytochrome P-450 CYP1A1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1) RN - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases) RN - EC 2.1.1.37 (Dnmt1 protein, mouse) RN - EC 2.3.1.48 (p300-CBP Transcription Factors) RN - EC 3.5.1.98 (Hdac1 protein, mouse) RN - EC 3.5.1.98 (Histone Deacetylase 1) RN - EC 3.5.1.98 (Histone Deacetylases) SB - IM MH - Acetylation MH - Animals MH - Benzo(a)pyrene/metabolism MH - Carrier Proteins/genetics/metabolism MH - Catalysis MH - Cell Line, Tumor MH - Chromatin Assembly and Disassembly/physiology MH - Cytochrome P-450 CYP1A1/*biosynthesis MH - DNA (Cytosine-5-)-Methyltransferase 1 MH - DNA (Cytosine-5-)-Methyltransferases/metabolism MH - Enzyme Induction/physiology MH - Enzyme Repression/physiology MH - Fetal Proteins/genetics/metabolism MH - Histone Deacetylase 1 MH - Histone Deacetylases/*metabolism MH - Histones/*metabolism MH - Methylation MH - Mice MH - Microtubule-Associated Proteins MH - Phosphorylation MH - Promoter Regions, Genetic/*physiology MH - Protein Binding/physiology MH - Protein Processing, Post-Translational/physiology MH - Receptors, Aryl Hydrocarbon/*metabolism MH - Transcriptional Activation/*physiology MH - p300-CBP Transcription Factors PMC - PMC2083643 MID - NIHMS31273 EDAT- 2007/08/21 09:00 MHDA- 2007/12/06 09:00 PMCR- 2008/09/01 CRDT- 2007/08/21 09:00 PHST- 2007/05/25 00:00 [received] PHST- 2007/07/12 00:00 [revised] PHST- 2007/07/12 00:00 [accepted] PHST- 2007/08/21 09:00 [pubmed] PHST- 2007/12/06 09:00 [medline] PHST- 2007/08/21 09:00 [entrez] PHST- 2008/09/01 00:00 [pmc-release] AID - S0167-4781(07)00123-6 [pii] AID - 10.1016/j.bbaexp.2007.07.002 [doi] PST - ppublish SO - Biochim Biophys Acta. 2007 Sep-Oct;1769(9-10):569-78. doi: 10.1016/j.bbaexp.2007.07.002. Epub 2007 Jul 20.