ArticleGenome medicine2018
Integrative analysis reveals functional and regulatory roles of H3K79me2 in mediating alternative splicing.
Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 67 citations in OpenAlex.
- Article
- Functional regulatory mechanisms of circRNAs in bovine adipogenesis.Cytotechnology · 2025Review
- Article
- The crosstalk between alternative splicing and circular RNA in cancer: pathogenic insights and therapeutic implications.Cellular & molecular biology letters · 2024Review
- Nucleophosmin 1 cooperates with the methyltransferase DOT1L to preserve peri-nucleolar heterochromatin organization by regulating H3K27me3 levels and DNA repeats expression.Epigenetics & chromatin · 2023Article
- The risk model construction of the genes regulated by H3K36me3 and H3K79me2 in breast cancer.Biophysics reports · 2023Article
- Bioinformatic Analyses of Broad H3K79me2 Domains in Different Leukemia Cell Line Data Sets.Cells · 2022Article
- Histone Marks-Dependent Effect on Alternative Splicing: New Perspectives for Targeted Splicing Modulation in Cancer?International journal of molecular sciences · 2022Review
- Alternative Splicing, Epigenetic Modifications and Cancer: A Dangerous Triangle, or a Hopeful One?Cancers · 2022Review
- Chromatin loop anchors predict transcript and exon usage.Briefings in bioinformatics · 2021Article
- NucHMM: a method for quantitative modeling of nucleosome organization identifying functional nucleosome states distinctly associated with splicing potentiality.Genome biology · 2021Article
- Genomic variation, origin tracing, and vaccine development of SARS-CoV-2: A systematic review.Innovation (Cambridge (Mass.)) · 2021Review
- Splicing-associated chromatin signatures: a combinatorial and position-dependent role for histone marks in splicing definition.Nature communications · 2021Article
- Histone modifications during the life cycle of the brown alga Ectocarpus.Genome biology · 2021Article
- Hydroxyphenyl Butanone Induces Cell Cycle Arrest through Inhibition of GSK3BioMed research international · 2021Article
- Potential Drug Prediction of Glioblastoma Based on Drug Perturbation-Induced Gene Expression Signatures.BioMed research international · 2021Article
- The Crosstalk Between Epigenetic Mechanisms and Alternative RNA Processing Regulation.Frontiers in genetics · 2020Review
- The eIF2α Kinase GCN2 Modulates Period and Rhythmicity of the Circadian Clock by Translational Control of Atf4.Neuron · 2019Article
- The histone methyltransferase DOT1L is required for proper DNA damage response, DNA repair, and modulates chemotherapy responsiveness.Clinical epigenetics · 2019Article
- Not Only Mutations Matter: Molecular Picture of Acute Myeloid Leukemia Emerging from Transcriptome Studies.Journal of oncology · 2019Review
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundAccumulating evidence suggests alternative splicing (AS) is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic regulators, such as chromatin structure, nucleosome density, and histone modification. Aberrant AS plays an important role in regulating various diseases, including cancers.
methodsIn this study, we integrated AS events derived from RNA-seq with H3K79me2 ChIP-seq data across 34 different normal and cancer cell types and found the higher enrichment of H3K79me2 in two AS types, skipping exon (SE) and alternative 3' splice site (A3SS).
resultsInterestingly, by applying self-organizing map (SOM) clustering, we unveiled two clusters mainly comprised of blood cancer cell types with a strong correlation between H3K79me2 and SE. Remarkably, the expression of transcripts associated with SE was not significantly different from that of those not associated with SE, indicating the involvement of H3K79me2 in splicing has little impact on full mRNA transcription. We further showed that the deletion of DOT1L1, the sole H3K79 methyltransferase, impeded leukemia cell proliferation as well as switched exon skipping to the inclusion isoform in two MLL-rearranged acute myeloid leukemia cell lines. Our data demonstrate H3K79me2 was involved in mediating SE processing, which might in turn influence transformation and disease progression in leukemias.
conclusionsCollectively, our work for the first time reveals that H3K79me2 plays functional and regulatory roles through a co-transcriptional splicing mechanism.
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