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


Journal

Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011

Informations de publication

Date de publication:
09 07 2019
Historique:
accepted: 27 04 2019
revised: 17 04 2019
received: 01 05 2018
pubmed: 12 5 2019
medline: 26 2 2020
entrez: 12 5 2019
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 31076740
pii: 5488017
doi: 10.1093/nar/gkz338
pmc: PMC6614845
doi:

Substances chimiques

Chromatin 0
H1-5 protein, human 0
Histones 0
RNA Splice Sites 0
DNA 9007-49-2
RNA Polymerase II EC 2.7.7.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

6145-6159

Informations de copyright

© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

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Auteurs

Ohad Glaich (O)

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

Yodfat Leader (Y)

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

Galit Lev Maor (G)

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

Gil Ast (G)

Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv 69978, Israel.

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Classifications MeSH