OXR1A, a Coactivator of PRMT5 Regulating Histone Arginine Methylation

被引：24

作者：

Yang, Mingyi ^{[1
,2
,3
]}

Lin, Xiaolin ^{[1
,2
,3
]}

Segers, Filip ^{[3
,4
]}

Suganthan, Rajikala ^{[1
]}

Hildrestrand, Gunn A. ^{[1
]}

Rinholm, Johanne E. ^{[1
]}

Aas, Per Arne ^{[6
]}

Sousa, Mirta M. L. ^{[6
,9
,10
]}

Holm, Sverre ^{[3
,4
]}

Bolstad, Nils ^{[2
,3
]}

Warren, David ^{[2
,3
]}

Berge, Rolf K. ^{[7
,8
]}

Johansen, Rune F. ^{[1
]}

Yndestad, Arne ^{[3
,4
]}

Kristiansen, Elise ^{[1
]}

Klungland, Arne ^{[1
]}

Luna, Luisa ^{[1
]}

Eide, Lars ^{[2
,3
]}

Halvorsen, Bente ^{[3
,4
]}

Aukrust, Pal ^{[3
,4
,5
]}

Bjoras, Magnar ^{[1
,2
,3
,6
,9
]}

机构：

[1] Oslo Univ Hosp, Dept Microbiol, Oslo, Norway

[2] Oslo Univ Hosp, Dept Med Biochem, Oslo, Norway

[3] Univ Oslo, Oslo, Norway

[4] Oslo Univ Hosp, Res Inst Internal Med, Oslo, Norway

[5] Oslo Univ Hosp, Sect Clin Immunol & Infect Dis, Oslo, Norway

[6] Norwegian Univ Sci & Technol, Dept Clin & Mol Med, Trondheim, Norway

[7] Univ Bergen, Dept Clin Sci, Bergen, Norway

[8] Haukeland Hosp, Dept Heart Dis, Bergen, Norway

[9] St Olavs Hosp, Dept Lab Med, Trondheim, Norway

[10] Norwegian Univ Sci & Technol, Cent Norway Reg Hlth Author, Prote & Metabol Core Facil PROMEC, Trondheim, Norway

来源：

CELL REPORTS | 2020年 / 30卷 / 12期

关键词：

GROWTH-HORMONE; SYMMETRIC DIMETHYLATION; OXIDATIVE STRESS; PROTEIN; CELLS; H3R2; METHYLTRANSFERASE; METABOLISM; ACTIVATION; EXPRESSION;

D O I：

10.1016/j.celrep.2020.02.063

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：4165 / +

页数：21

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