Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition [ChIP-Seq]

ABSTRACT: Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs) and inhibiting DNA methylation results in aberrant splicing of ASEs. The methyl-CpG binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly DNA methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased nucleosome acetylation and aberrant skipping events of ASEs. We further show that inhibition of histone deacetylases leads to a highly significant overlap of exon skipping events caused by knocking-down MeCP2. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through its established interaction with HDACs. MeCP2 ChIP-Seq in IMR90 and HCT116 cells

ORGANISM(S): Homo sapiens

SUBMITTER: Iouri Chepelev

PROVIDER: E-GEOD-47677 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition.

Maunakea Alika K AK Chepelev Iouri I Cui Kairong K Zhao Keji K

Cell research 20130813 11

Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs), and that inhibition of DNA methylation results in aberrant splicing of ASEs. The methyl-CpG-binding protein MeCP2 is enriched in included ASEs, pa ...[more]

PMID: 23938295

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Project description:DNA methylation is a dynamic process through which specific chromatin modifications can be stably transmitted from parent to daughter cells. A large body of work has suggested that DNA methylation influences gene expression by silencing gene promoters. However, these conclusions were drawn from data focused mostly on promoter regions. With regards to the entire genome, it is unclear how methylation and gene transcription patterns are related during vertebrate development. To identify the genome-wide distribution of CpG methylation we created series of high-resolution methylome maps of Danio rerio embryos during development and in mature, differentiated tissues. We find that embryonic and terminal tissues have unique methylation signatures in CpG islands and repetitive sequences. Fully differentiated tissues have increased CpG and LTR methylation and decreased SINE methylation relative to embryonic tissues. Unsupervised clustering analyses reveal that the embryonic and terminal tissues can be classified solely by their methylation patterning. Novel analyses also identify a previously undescribed genome-wide exon methylation signature. We also compared whole genome methylation with genome-wide mRNA expression levels using publicly available RNA-seq datasets. These comparisons revealed previously unrecognized relationships between gene-expression, alternative splicing and exon methylation. Surprisingly, we find that exonic methylation is a better predictor of mRNA expression level than promoter methylation. We also found that transcriptionally skipped exons have significantly less methylation than retained exons. Our integrative analyses reveal highly complex interplay between gene expression, alternative splicing, development, and methylation patterning in zebrafish. MBD-Seq with whole embryos (sperm, 1cell, mbt, 3dpf) and adult tissues (eye, brain, heart, liver) Please note that the mePoor brain lane4 sample raw data files were used as loading/sequencing controls for the following meRich.lane4 samples; eye_meRich.lane4 heart_meRich.lane4 liver_meRich.lane4 The mePoor brain lane5 sample raw data files were used as loading/sequencing controls for the following meRich.lane5 samples; 1cell_meRich.lane5 mbt_meRich.lane5 sperm_meRich.lane5

Dataset Information

Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition [ChIP-Seq]

Publications

Intragenic DNA methylation modulates alternative splicing by recruiting MeCP2 to promote exon recognition.

Similar Datasets

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