Histone H1.5 binds over splice sites in chromatin and regulates alternative splicing

Ohad Glaich, Yodfat Leader, Galit Lev Maor, Gil Ast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Chromatin organization and epigenetic markers influence splicing, though the magnitudes of these effects and the mechanisms are largely unknown. Here, we demonstrate that linker histone H1.5 influences mRNA splicing. We observed that linker histone H1.5 binds DNA over splice sites of short exons in human lung fibroblasts (IMR90 cells). We found that association of H1.5 with these splice sites correlated with the level of inclusion of alternatively spliced exons. Exons marked by H1.5 had more RNA polymerase II (RNAP II) stalling near the 3 splice site than did exons not associated with H1.5. In cells depleted of H1.5, we showed that the inclusion of five exons evaluated decreased and that RNAP II levels over these exons were also reduced. Our findings indicate that H1.5 is involved in regulation of splice site selection and alternative splicing, a function not previously demonstrated for linker histones.

Original languageEnglish
Pages (from-to)6145-6159
Number of pages15
JournalNucleic Acids Research
Volume47
Issue number12
DOIs
StatePublished - 8 Jul 2019

Funding

FundersFunder number
Edmond J. Safra Bioinformatics Center
German-Israel foundation for R&DGIF I-1460
Ministry of Science and Technology R&D Israel-German3-13112
United States-Israel Binational Science FoundationBSF 2017086
Israel Science FoundationISF 671/18, ISF 142/13
Tel Aviv University142/13

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