The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G

Leisegang, Matthias S.1,2; Gu, Lunda1; Preussner, Jens2,3; Guenther, Stefan2,3; Hitzel, Juliane1,2; Ratiu, Corina1,4; Weigert, Andreas5; Chen, Wei2,6,7; Schwarz, Eva C.8; Looso, Mario2,3; Fork, Christian1,2; Brandes, Ralf P.1,2

2019-03

10.1002/1873-3468.13337

FEBS LETTERS   影响因子和分区

0014-5793

1873-3468

Histone3-lysine9 (H3K9) residues not only control gene expression, but also contribute to RNA splicing. Here, the H3K9 histone demethylase PHF8 was investigated in endothelial cells for its involvement in alternative splicing. An angiogenic sprouting assay shows the importance of PHF8 for endothelial cells. Immunoprecipitation reveals that PHF8 interacts with U1 spliceosomal proteins, such as SRPK1 and snRNP70. We identify the histocompatibility antigen HLA-G as a target of PHF8. The inclusion of HLA-G intron 4, with concomitant RNA Polymerase II accumulation at this intron is controlled by PHF8 and H3K9. Soluble HLA-G is generated after PHF8 knockdown, which leads to reduced T-cell proliferation. Collectively, PHF8 knockdown generates the immunosuppressive alternative splice product soluble HLA-G, which is secreted by endothelial cells to elicit a potential inhibitory effect on inflammation.

endothelium epigenetics HLA-G PHF8 splicing

SCI

英语

其他

DFG[Sonderforschungsbereiche SFB834] ; DFG[SFB1039] ; DFG[SFB894]

Biochemistry & Molecular Biology ; Biophysics ; Cell Biology

Biochemistry & Molecular Biology ; Biophysics ; Cell Biology

WOS:000461017900003

WILEY

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Goethe Univ, Inst Cardiovasc Physiol, Med Fac, Frankfurt, Germany
2.German Ctr Cardiovasc Res DZHK, Partner Site RheinMain, Frankfurt, Germany
3.Max Planck Inst Heart & Lung Res, ECCPS Bioinformat & Sequencing Facil, Bad Nauheim, Germany
4.Victor Babes Univ Med & Pharm Timisoara, Dept Funct Sci Pathophysiol, Timisoara, Romania
5.Goethe Univ, Inst Biochem 1, Fac Med, Frankfurt, Germany
6.Max Delbruck Ctr Mol Med, Lab Novel Sequencing Technol Funct & Med Genom, Berlin, Germany
7.Southern Univ Sci & Technol, Dept Biol, Shenzhen, Peoples R China
8.Saarland Univ, Sch Med, Ctr Integrat Physiol & Mol Med, Biophys, Homburg, Germany

Leisegang, Matthias S.,Gu, Lunda,Preussner, Jens,et al. The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G[J]. FEBS LETTERS,2019,593(5):487-498.

Leisegang, Matthias S..,Gu, Lunda.,Preussner, Jens.,Guenther, Stefan.,Hitzel, Juliane.,...&Brandes, Ralf P..(2019).The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G.FEBS LETTERS,593(5),487-498.

Leisegang, Matthias S.,et al."The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G".FEBS LETTERS 593.5(2019):487-498.