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

Item Type:	Article
Title:	The histone demethylase PHF8 facilitates alternative splicing of the histocompatibility antigen HLA-G
Creators Name:	Leisegang, M.S. and Gu, L. and Preussner, J. and Günther, S. and Hitzel, J. and Ratiu, C. and Weigert, A. and Chen, W. and Schwarz, E.C. and Looso, M. and Fork, C. and Brandes, R.P.
Abstract:	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.
Keywords:	Endothelium, Epigenetics, HLA-G, PHF8, Splicing
Source:	FEBS Letters
ISSN:	0014-5793
Publisher:	Wiley-Blackwell
Volume:	593
Number:	5
Page Range:	487-498
Date:	March 2019
Official Publication:	https://doi.org/10.1002/1873-3468.13337
PubMed:	View item in PubMed

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