title: PARP-2 regulates cell cycle-related genes through histone deacetylation and methylation independently of poly(ADP-ribosyl)ation.
abstract: Poly(ADP-ribose) polymerase-2 (PARP-2) catalyzes poly(ADP-ribosyl)ation (PARylation) and regulates numerous nuclear processes, including transcription. Depletion of PARP-2 alters the activity of transcription factors and global gene expression. However, the molecular action of how PARP-2 controls the transcription of target promoters remains unclear. Here we report that PARP-2 possesses transcriptional repression activity independently of its enzymatic activity. PARP-2 interacts and recruits histone deacetylases HDAC5 and HDAC7, and histone methyltransferase G9a to the promoters of cell cycle-related genes, generating repressive chromatin signatures. Our findings propose a novel mechanism of PARP-2 in transcriptional regulation involving specific protein-protein interactions and highlight the importance of PARP-2 in the regulation of cell cycle progression.
authors.affiliation: Institute of Molecular Biology, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Ya-Chen
authors.initials: YC
authors.lastname: Liang
authors.forename: Chiao-Yu
authors.initials: CY
authors.lastname: Hsu
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Yao
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Yang
mesh_terms: D002453:Cell Cycle / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006649:Histocompatibility Antigens / Q000378:metabolism; D006655:Histone Deacetylases / Q000378:metabolism; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: D006649:Histocompatibility Antigens; D006657:Histones; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D011064:Poly Adenosine Diphosphate Ribose; C445405:EHMT2 protein, human; D011495:Histone-Lysine N-Methyltransferase; C483041:PARP2 protein, human; D011065:Poly(ADP-ribose) Polymerases; C404500:HDAC5 protein, human; C543273:HDAC7 protein, human; D006655:Histone Deacetylases