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The histone demethylase PHF 8 facilitates alternative splicing of the histocompatibility antigen HLA ‐G
Author(s) -
Leisegang Matthias S.,
Gu Lunda,
Preussner Jens,
Günther Stefan,
Hitzel Juliane,
Ratiu Corina,
Weigert Andreas,
Chen Wei,
Schwarz Eva C.,
Looso Mario,
Fork Christian,
Brandes Ralf P.
Publication year - 2019
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13337
Subject(s) - demethylase , intron , rna splicing , gene knockdown , microbiology and biotechnology , chemistry , human leukocyte antigen , immunoprecipitation , alternative splicing , rna , rna binding protein , histone , major histocompatibility complex , antigen , biology , exon , gene , immunology , biochemistry
Histone3‐lysine9 (H3K9) residues not only control gene expression, but also contribute to RNA splicing. Here, the H3K9 histone demethylase PHF 8 was investigated in endothelial cells for its involvement in alternative splicing. An angiogenic sprouting assay shows the importance of PHF 8 for endothelial cells. Immunoprecipitation reveals that PHF 8 interacts with U1 spliceosomal proteins, such as SRPK 1 and sn RNP 70. We identify the histocompatibility antigen HLA ‐G as a target of PHF 8. The inclusion of HLA ‐G intron 4, with concomitant RNA Polymerase II accumulation at this intron is controlled by PHF 8 and H3K9. Soluble HLA ‐G is generated after PHF 8 knockdown, which leads to reduced T‐cell proliferation. Collectively, PHF 8 knockdown generates the immunosuppressive alternative splice product soluble HLA ‐G, which is secreted by endothelial cells to elicit a potential inhibitory effect on inflammation.
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