In:
FEBS Letters, Wiley, Vol. 593, No. 5 ( 2019-03), p. 487-498
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0014-5793
,
1873-3468
DOI:
10.1002/feb2.2019.593.issue-5
DOI:
10.1002/1873-3468.13337
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2019
ZDB Id:
1460391-3
SSG:
12