Cell systems, 2017-12, Vol.5 (6), p.628-637.e6
2017
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Details
- Autor(en) / Beteiligte
- Titel
- CTCF-Mediated Chromatin Loops between Promoter and Gene Body Regulate Alternative Splicing across Individuals
- Ist Teil von
- Cell systems, 2017-12, Vol.5 (6), p.628-637.e6
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2017
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- The CCCTC-binding factor (CTCF) is known to establish long-range DNA contacts that alter the three-dimensional architecture of chromatin, but how the presence of CTCF influences nearby gene expression is still poorly understood. Here, we analyze CTCF chromatin immunoprecipitation sequencing, RNA sequencing, and Hi-C data, together with genotypes from a healthy human cohort, and measure statistical associations between inter-individual variability in CTCF binding and alternative exon usage. We demonstrate that CTCF-mediated chromatin loops between promoters and intragenic regions are prevalent and that when exons are in physical proximity with their promoters, CTCF binding correlates with exon inclusion in spliced mRNA. Genome-wide, CTCF-bound exons are enriched for genes involved in signaling and cellular stress-response pathways. Structural analysis of three specific examples, checkpoint kinase 2 (CHK2), CDC-like kinase 3 (CLK3), and euchromatic histone-lysine N-methyltransferase (EHMT1), suggests that CTCF-mediated exon inclusion is likely to downregulate enzyme activity by disrupting annotated protein domains. In total, our study suggests that alternative exon usage is regulated by CTCF-dependent chromatin structure. [Display omitted] •CTCF-mediated intragenic looping can regulate alternative exon usage•Genetic variation that affects CTCF looping leads to variation in splice isoforms•Genes regulated by CTCF loops are involved in signaling and cellular stress response The presence of CTCF-mediated intragenic chromatin loops regulates alternative splicing; this, in turn, may impact cellular decision making.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2405-4712eISSN: 2405-4720DOI: 10.1016/j.cels.2017.10.018Titel-ID: cdi_proquest_miscellaneous_1972305537
- Format
- –
- Schlagworte
- 3D organization, alternative exon usage, Alternative Splicing, CCCTC-Binding Factor - genetics, Checkpoint Kinase 2 - genetics, Checkpoint Kinase 2 - metabolism, Chromatin - genetics, Chromatin - metabolism, chromatin loops, chromatin structure, Computational Biology, CTCF, Exons - genetics, Gene Expression Regulation, gene regulation, genetic variation, Genome, Histone-Lysine N-Methyltransferase - genetics, Histone-Lysine N-Methyltransferase - metabolism, Humans, Observer Variation, Promoter Regions, Genetic - genetics, Protein Binding, Protein-Serine-Threonine Kinases - genetics, Protein-Serine-Threonine Kinases - metabolism, Protein-Tyrosine Kinases - genetics, Protein-Tyrosine Kinases - metabolism, Signal Transduction - genetics, Stress, Physiological - genetics, Structure-Activity Relationship