論文 - 詳細
| RRC ID | 88286 |
|---|---|
| 著者 | Bricambert J, Alves-Guerra MC, Esteves P, Prip-Buus C, Bertrand-Michel J, Guillou H, Chang CJ, Vander Wal MN, Canonne-Hergaux F, Mathurin P, Raverdy V, Pattou F, Girard J, Postic C, Dentin R. |
| タイトル | The histone demethylase Phf2 acts as a molecular checkpoint to prevent NAFLD progression during obesity. |
| ジャーナル | Nat Commun |
| Abstract |
Aberrant histone methylation profile is reported to correlate with the development and progression of NAFLD during obesity. However, the identification of specific epigenetic modifiers involved in this process remains poorly understood. Here, we identify the histone demethylase Plant Homeodomain Finger 2 (Phf2) as a new transcriptional co-activator of the transcription factor Carbohydrate Responsive Element Binding Protein (ChREBP). By specifically erasing H3K9me2 methyl-marks on the promoter of ChREBP-regulated genes, Phf2 facilitates incorporation of metabolic precursors into mono-unsaturated fatty acids, leading to hepatosteatosis development in the absence of inflammation and insulin resistance. Moreover, the Phf2-mediated activation of the transcription factor NF-E2-related factor 2 (Nrf2) further reroutes glucose fluxes toward the pentose phosphate pathway and glutathione biosynthesis, protecting the liver from oxidative stress and fibrogenesis in response to diet-induced obesity. Overall, our findings establish a downstream epigenetic checkpoint, whereby Phf2, through facilitating H3K9me2 demethylation at specific gene promoters, protects liver from the pathogenesis progression of NAFLD. |
| 巻・号 | 9(1) |
| ページ | 2092 |
| 公開日 | 2018-5-29 |
| DOI | 10.1038/s41467-018-04361-y |
| PII | 10.1038/s41467-018-04361-y |
| PMID | 29844386 |
| PMC | PMC5974278 |
| MeSH | Animals Basic Helix-Loop-Helix Leucine Zipper Transcription Factors Cells, Cultured Demethylation* Enzyme Activation Glucose / metabolism Glutathione / biosynthesis Histone Demethylases / metabolism* Histones / metabolism* Homeodomain Proteins / metabolism* Humans Liver / pathology Male Methylation Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 / metabolism* Non-alcoholic Fatty Liver Disease / pathology* Nuclear Proteins / genetics Nuclear Proteins / metabolism* Obesity / pathology* Oxidative Stress / genetics Oxidative Stress / physiology Pentose Phosphate Pathway / physiology Promoter Regions, Genetic / genetics Transcription Factors / genetics Transcription Factors / metabolism* |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 11 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01390 |