title: Novel mechanism of negative regulation of 1,25-dihydroxyvitamin D3-induced 25-hydroxyvitamin D3 24-hydroxylase (Cyp24a1) Transcription: epigenetic modification involving cross-talk between protein-arginine methyltransferase 5 and the SWI/SNF complex.
abstract: The SWI/SNF chromatin remodeling complex facilitates gene transcription by remodeling chromatin using the energy of ATP hydrolysis. Recent studies have indicated an interplay between the SWI/SNF complex and protein-arginine methyltransferases (PRMTs). Little is known, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription. Using SWI/SNF-defective cells, we demonstrated that Brahma-related gene 1 (BRG1), an ATPase that is a component of the SWI/SNF complex, plays a fundamental role in induction by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) of the transcription of Cyp24a1 encoding the enzyme 25-hydroxyvitamin D3 24-hydroxylase involved in the catabolism of 1,25(OH)2D3. BRG1 was found to associate with CCAAT-enhancer-binding protein (C/EBP) β and cooperate with VDR and C/EBPβ in regulating Cyp24a1 transcription. PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcription and mRNA expression. Our findings indicate the requirement of the C/EBP site for the inhibitory effect of PRMT5 via its methylation of H3R8 and H4R3. These findings indicate that the SWI/SNF complex and PRMT5 may be key factors involved in regulation of 1,25(OH)2D3 catabolism and therefore in the maintenance of calcium homeostasis by vitamin D. These studies also define epigenetic events linked to a novel mechanism of negative regulation of VDR-mediated transcription.
authors.affiliation: From the Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey 07103 and.
authors.forename: Tanya
authors.initials: T
authors.lastname: Seth-Vollenweider
authors.affiliation: From the Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey 07103 and.
authors.forename: Sneha
authors.initials: S
authors.lastname: Joshi
authors.affiliation: From the Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey 07103 and.
authors.forename: Puneet
authors.initials: P
authors.lastname: Dhawan
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210.
authors.forename: Said
authors.initials: S
authors.lastname: Sif
authors.affiliation: From the Department of Microbiology, Biochemistry, and Molecular Genetics, New Jersey Medical School, Rutgers-The State University of New Jersey, Newark, New Jersey 07103 and christak@njms.rutgers.edu.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Christakos
mesh_terms: D000818:Animals; D019556:COS Cells; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D025461:Feedback, Physiological; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases; D002117:Calcitriol; D002118:Calcium
keywords: CCAAT-Enhancer-binding Protein (C/EBP); CYP24A1; Calcium; Protein-arginine N-Methyltransferase 5 (PRMT5); SWI/SNF; Transcription; Transcription Corepressor; Vitamin D; Vitamin D Receptor