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Metadata

Name
DNA methylation regulates intron retention via altered MeCP2-mediated splicing factor recruitment
Repository
Gene Expression Omnibus
Identifier
geo.series:GSE85517
Description
While intron retention (IR) is now recognized as a widespread and conserved mechanism of gene expression control, its regulation is poorly understood. Here, we identify significantly reduced DNA methylation levels near splice junctions flanking retained introns compared to non-retained introns in diverse primary cells and cell lines. Further, we identify increased IR following inhibition of DNA methylation indicating that reduced DNA methylation promotes IR. We demonstrate reduced occupancy of MeCP2 near the splice junctions of retained introns, mirroring the reduced DNA methylation at these sites. Accordingly, MeCP2 depletion in tissues/cells enhances IR. By analyzing the MeCP2 interactome, we demonstrate that decreased MeCP2 binding near splice junctions facilitates IR via reduced recruitment of the splicing factor, Tra2b, and increased RNA polymerase II stalling. Our study identifies a dynamic interplay between DNA methylation, MeCP2 and splicing factors including Tra2b in IR regulation and provides novel insights into the mechanisms governing splicing.
Data or Study Types
Methylation profiling by high throughput sequencing, Genome binding/occupancy profiling by high throughput sequencing
Source Organization
National Center for Biotechnology Information
Access Conditions
available
Year
2017
Access Hyperlink
http://www.ncbi.nlm.nih.gov/sites/GDSbrowser?acc=GSE85517

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