Histone H3 lysine 9 trimethylation and HP1γ favor inclusion of alternative exons
Abstract
Pre-messenger RNAs (pre-mRNAs) maturation is initiated cotranscriptionally. It is therefore conceivable that chromatin-borne information participates in alternative splicing. Here we find that elevated levels of trimethylation of histone H3 on Lys9 (H3K9me3) are a characteristic of the alternative exons of several genes including CD44. On this gene the chromodomain protein HP1γ, frequently defined as a transcriptional repressor, facilitates inclusion of the alternative exons via a mechanism involving decreased RNA polymerase II elongation rate. In addition, accumulation of HP1γ on the variant region of the CD44 gene stabilizes association of the pre-mRNA with the chromatin. Altogether, our data provide evidence for localized histone modifications impacting alternative splicing. They further implicate HP1γ as a possible bridging molecule between the chromatin and the maturating mRNA, with a general impact on splicing decisions.
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HP1γ has been suggested to locally increase RNA Pol II pausing on alternatively spliced exons enriched in H3K9me3 marks.
“Through RNA Pol II ChIP measurements, HP1γ has been suggested to locally increase RNA Pol II pausing on alternatively spliced exons enriched in H3K9me3 marks (Saint‐André et al, 2011).”
From RNA polymerase II speed: a key player in controlling and adapting transcriptome composition (2021) · cites this paper as Saint‐André et al, 2011
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- Authors
- Saint-André, V., Batsché, E., Rachez, C., & Muchardt, C.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Corresponding author
- Muchardt, Christian
- Venue
- Nature Structural & Molecular Biology
- Published
- 2011-02-27
- Volume
- 18
- Issue
- 3
- Pages
- 337-344
- ISSN
- 1545-9985 (ISSN-L)
- 1545-9993
- OpenAlex
- W2015332493
- Cited by
- 278
- References
- 3
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 12 · 2023: 21 · 2022: 18 · 2021: 15 · 2020: 12 · 2019: 21 · 2018: 19 · 2017: 21 · 2016: 11 · 2015: 34 · 2014: 30 · 2013: 15 · 2012: 24
- FWCI
- 10.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Structural & Molecular Biology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- alternative splicing, H3K9 trimethylation, H3K9, HP1γ, chromodomain protein, CD44, RNA polymerase II elongation, pre-mRNA splicing, chromatin, co-transcriptional splicing, histone modifications
- MeSH terms
- Cell Line, Chromosomal Proteins, Non-Histone, Exons, HeLa Cells, Histones, Humans, Lysine, Methylation, RNA Polymerase II, RNA Precursors, Alternative Splicing, Hyaluronan Receptors
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