The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
HP1 Is Involved in Regulating the Global Impact of DNA Methylation on Alternative Splicing
Open accessAbstract
The global impact of DNA methylation on alternative splicing is largely unknown. Using a genome-wide approach in wild-type and methylation-deficient embryonic stem cells, we found that DNA methylation can either enhance or silence exon recognition and affects the splicing of more than 20% of alternative exons. These exons are characterized by distinct genetic and epigenetic signatures. Alternative splicing regulation of a subset of these exons can be explained by heterochromatin protein 1 (HP1), which silences or enhances exon recognition in a position-dependent manner. We constructed an experimental system using site-specific targeting of a methylated/unmethylated gene and demonstrate a direct causal relationship between DNA methylation and alternative splicing. HP1 regulates this gene's alternative splicing in a methylation-dependent manner by recruiting splicing factors to its methylated form. Our results demonstrate DNA methylation's significant global influence on mRNA splicing and identify a specific mechanism of splicing regulation mediated by HP1.
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Cites
Alternative isoform regulation in human tissue transcriptomes
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Human DNA methylomes at base resolution show widespread epigenomic differences
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DNA methylation: roles in mammalian development
Smith, Z. D., & Meissner, A. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3354 · Cited by 3,045
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing
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The Honey Bee Epigenomes: Differential Methylation of Brain DNA in Queens and Workers
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Chromatin organization marks exon-intron structure
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Self-citationMaunakea, A. K., Chepelev, I., Cui, K., & Zhao, K. (2013) · Cell Research · doi:10.1038/cr.2013.110 · Cited by 552
DNA methylation contributes to natural human variation
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Control of alternative splicing through siRNA-mediated transcriptional gene silencing
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Cited by
Intragenic DNA methylation prevents spurious transcription initiation
Neri, F., Rapelli, S., Krepelova, A., Incarnato, D., Parlato, C., Basile, G., Maldotti, M., Anselmi, F., & Oliviero, S. (2017) · Nature · doi:10.1038/nature21373 · Cited by 739
The alternative role of DNA methylation in splicing regulation
Lev Maor, G., Yearim, A., & Ast, G. (2015) · Trends in Genetics · doi:10.1016/j.tig.2015.03.002 · Cited by 567
Self-citationRegulation of Alternative Splicing Through Coupling with Transcription and Chromatin Structure
Naftelberg, S., Schor, I. E., Ast, G., & Kornblihtt, A. R. (2015) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060614-034242 · Cited by 448
Self-citationZhou, L., Tian, S., & Qin, G. (2019) · Genome Biology · doi:10.1186/s13059-019-1771-7 · Cited by 382
Evolution of DNA Methylation across Insects
Bewick, A. J., Vogel, K. J., Moore, A. J., & Schmitz, R. J. (2016) · Molecular Biology and Evolution · doi:10.1093/molbev/msw264 · Cited by 353
Metadata
- Authors
- Yearim, A., Gelfman, S., Shayevitch, R., Melcer, S., Glaich, O., Mallm, J.-P., Nissim-Rafinia, M., Cohen, A.-H. S., Rippe, K., Meshorer, E., & Ast, G.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 10
- Issue
- 7
- Pages
- 1122-1134
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W2021183579
- Cited by
- 218
- References
- 15
- FWCI
- 10.16
- Type
- journal article
- Language
- en
- Open access
- gold
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- Yearim, A., Gelfman, S., Shayevitch, R., Melcer, S., Glaich, O., Mallm, J.-P., Nissim-Rafinia, M., Cohen, A.-H. S., Rippe, K., Meshorer, E., & Ast, G. (2015). HP1 Is Involved in Regulating the Global Impact of DNA Methylation on Alternative Splicing. Cell Reports. https://doi.org/10.1016/j.celrep.2015.01.038
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