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MeCP2 regulates genome-wide gene expression through recognition of H3K27me3 [ChIP_human]

ABSTRACT: MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA to regulate gene expression is well established. However, the widespread MeCP2 distribution suggests its additional interactions with chromatin. Here we show, by both biochemical and ChIP-seq analyses, that MeCP2 directly binds to nucleosome subunit proteins and is recruited to distinct chromatin regions where H3K27me3 is enriched. We further observed that the impact of MeCP2 on transcriptional changes is correlated with histone post-translational modification patterns. Our findings indicate that MeCP2 can be recruited to genomic loci via indirect binding and that interaction between MeCP2 and histone proteins plays a significant role in gene expression regulation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE122364 | GEO | 2018/11/10

REPOSITORIES: GEO

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MeCP2 regulates genome-wide gene expression through recognition of H3K27me3 [NanoString]

Project description:MeCP2 plays a multifaceted role in gene expression regulation and chromatin organization. Interaction between MeCP2 and methylated DNA to regulate gene expression is well established. However, the widespread MeCP2 distribution suggests its additional interactions with chromatin. Here we show, by both biochemical and ChIP-seq analyses, that MeCP2 directly binds to nucleosome subunit proteins and is recruited to distinct chromatin regions where H3K27me3 is enriched. We further observed that the impact of MeCP2 on transcriptional changes is correlated with histone post-translational modification patterns. Our findings indicate that MeCP2 can be recruited to genomic loci via indirect binding and that interaction between MeCP2 and histone proteins plays a significant role in gene expression regulation.

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MeCP2 regulates gene expression through direct interaction with H3K27me3 [Targeted_BS_seq: DMSO_vs_GSK343]

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

Project description: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

2013-08-13 | E-GEOD-47677 | biostudies-arrayexpress

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

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

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

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MeCP2 interacts with chromosomal microRNAs in brain

Project description:Although methyl CpG binding domain protein-2 (MeCP2) is commonly understood to function as a silencing factor at methylated DNA sequences, recent studies also show that MeCP2 can bind unmethylated sequences and coordinate gene activation. MeCP2 displays broad binding patterns throughout the genome, with high expression levels similar to histone H1 in neurons. Despite its significant presence in the brain, only subtle gene expression changes occur in the absence of MeCP2. This may reflect a more complex regulatory mechanism of MeCP2 to complement chromatin binding. Using an RNA immunoprecipitation of native chromatin technique, we identify MeCP2 interacting microRNAs in mouse primary cortical neurons. In addition, comparison with mRNA sequencing data from Mecp2-null mice suggests that differentially expressed genes may indeed be targeted by MeCP2-interacting microRNAs. These findings highlight the MeCP2 interaction with microRNAs that may modulate its binding with chromatin and regulate gene expression.

2018-05-22 | GSE107085 | GEO

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