期刊
CELL REPORTS
卷 30, 期 12, 页码 4165-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.063
关键词
-
类别
资金
- South-East Health Authority [2014092, 2017117]
- Norwegian Cancer Society [182744-2016]
- Research Council of Norway [240099/F20, 24973, 239211]
Oxidation resistance gene 1 (OXR1) protects cells against oxidative stress. We find that male mice with brain-specific isoform A knockout (Oxr1A(-/-)) develop fatty liver. RNA sequencing of male Oxr1A(-/-) liver indicates decreased growth hormone (GH) signaling, which is known to affect liver metabolism. Indeed, Gh expression is reduced in male mice Oxr1A(-/-) pituitary gland and in rat Oxr1A(-/-) pituitary adenoma cell-line GH3. Oxr1A(-/-) male mice show reduced fasting-blood GH levels. Pulldown and proximity ligation assays reveal that OXR1A is associated with arginine methyl transferase PRMT5. OXR1A-depleted GH3 cells show reduced symmetrical dimethylation of histone H3 arginine 2 (H3R2me2s), a product of PRMT5 catalyzed methylation, and chromatin immunoprecipitation (ChIP) of H3R2me2s shows reduced Gh promoter enrichment. Finally, we demonstrate with purified proteins that OXR1A stimulates PRMT5/MEP50-catalyzed H3R2me2s. Our data suggest that OXR1A is a coactivator of PRMT5, regulating histone arginine methylation and thereby GH production within the pituitary gland.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据