The Peroxisome Proliferator-Activated Receptor γ/Retinoid X Receptor α Heterodimer Targets the Histone Modification Enzyme PR-Set7/Setd8 Gene and Regulates Adipogenesis through a Positive Feedback Loop
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- Ken-ichi Wakabayashi
- Genome Science Division
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- Masashi Okamura
- Metabolism and Endocrinology Division
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- Shuichi Tsutsumi
- Genome Science Division
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- Naoko S. Nishikawa
- Dynamical Bioinformatics Division
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- Toshiya Tanaka
- Metabolism and Endocrinology Division
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- Iori Sakakibara
- Metabolism and Endocrinology Division
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- Jun-ichi Kitakami
- Dynamical Bioinformatics Division
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- Sigeo Ihara
- Dynamical Bioinformatics Division
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- Yuichi Hashimoto
- Institute of Molecular & Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan
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- Takao Hamakubo
- Membrane Protein Division
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- Tatsuhiko Kodama
- Vascular System Division, Laboratory of Systems Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8904, Japan
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- Hiroyuki Aburatani
- Genome Science Division
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- Juro Sakai
- Metabolism and Endocrinology Division
説明
Control of cell differentiation occurs through transcriptional mechanisms and through epigenetic modification. Using a chromatin immunoprecipitation-on-chip approach, we performed a genome-wide search for target genes of peroxisome proliferator-activated receptor gamma (PPAR gamma) and its partner protein retinoid X receptor alpha during adipogenesis. We show that these two receptors target several genes that encode histone lysine methyltransferase SET domain proteins. The histone H4 Lys 20 (H4K20) monomethyltransferase PR-Set7/Setd8 gene is upregulated by PPAR gamma during adipogenesis, and the knockdown of PR-Set7/Setd8 suppressed adipogenesis. Intriguingly, monomethylated H4K20 (H4K20me1) levels are robustly increased toward the end of differentiation. PR-Set7/Setd8 positively regulates the expression of PPAR gamma and its targets through H4K20 monomethylation. Furthermore, the activation of PPAR gamma transcriptional activity leads to the induction of H4K20me1 modification of PPAR gamma and its targets and thereby promotes adipogenesis. We also show that PPAR gamma targets PPAR gamma2 and promotes its gene expression through H4K20 monomethylation. Our results connect transcriptional regulation and epigenetic chromatin modulation through H4K20 monomethylation during adipogenesis through a feedback loop.
収録刊行物
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- Molecular and Cellular Biology
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Molecular and Cellular Biology 29 (13), 3544-3555, 2009-07-01
Informa UK Limited
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キーワード
- Feedback, Physiological
- Adipogenesis
- Retinoid X Receptor alpha
- Transcription, Genetic
- Gene Expression Profiling
- Cell Differentiation
- Histone-Lysine N-Methyltransferase
- Microarray Analysis
- Histones
- Mice, Inbred C57BL
- PPAR gamma
- Mice
- Gene Expression Regulation
- 3T3-L1 Cells
- Animals
- Humans
- Obesity
- Promoter Regions, Genetic
- Protein Structure, Quaternary
- Dimerization
- Protein Binding
詳細情報 詳細情報について
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- CRID
- 1360846643400232192
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- ISSN
- 10985549
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- PubMed
- 19414603
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- KAKEN
- OpenAIRE