Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Junjie Guo
PROVIDER: E-GEOD-52331 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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2013-12-22 | E-GEOD-52330 | biostudies-arrayexpress
Project description:DNA methylation plays critical roles in the nervous system and has been traditionally considered to be restricted to CpG dinucleotides in metazoan genomes. Here we show that the single-base resolution neuronal DNA methylome from the adult mouse dentate gyrus consists of both CpG (~75%) and CpH (~25%) methylation (H = A/C/T). Neuronal CpH methylation is conserved in human brains, enriched in low CpG-density regions, depleted at protein-DNA interaction sites, and anti-correlated with gene expression. Functionally, both mCpGs and mCpHs can repress transcription in vitro and are recognized by MeCP2 in vivo. Unlike most CpG methylation, CpH methylation is established de novo during neuronal maturation and requires DNMT3A for active maintenance in post-mitotic neurons. These characteristics of CpH methylation suggest a significantly expanded proportion of the neuronal genome under cytosine methylation regulation and provide a new framework for understanding the roles of this key epigenetic modification in neuronal identity, maturation, plasticity and neurological disorders. Three biological replicates (dentate gyrus samples from C57Black6 mice) were analyzed by mRNA-seq
2013-12-22 | E-GEOD-52261 | biostudies-arrayexpress
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2014-03-06 | E-GEOD-53098 | biostudies-arrayexpress
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2014-11-14 | E-GEOD-58428 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation.We performed ChIP-seq analysis to investigate the role of AR and histone modifications.In addition, by siRNA mediated knockdown of AR-associated factors, changes of AR-binding sites in prostate cancer cells were analyzed.. ChIP-sequence analysis of AR and its associated factors in prostate cancer cells
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2013-07-24 | E-GEOD-42213 | biostudies-arrayexpress
Project description:The nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Examination of PIC, H3k4me3, Ctcf and Hnf4a occupancy in wild-type and Taf4-/- livers by deep sequencing
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Project description:Purpose: to characterize epigenetic changes following Twist1 mediated Epithelial-Mesenchymal Transition in human Methods: we characterized the epigenetic and transcriptome landscapes using whole genome transcriptome analysis by RNA-seq, DNA methylation by digital restriction enzyme analysis of methylation (DREAM) and histone modifications by CHIP-seq of H3K4me3 and H3K27me3 in immortalized human mammary epithelial cells relative to cells induced to undergo EMT by Twist1. Results: EMT is accompanied by focal hypermethylation and widespread global DNA hypomethylation, predominantly within transcriptionally repressed gene bodies. At the chromatin level, the number of gene promoters marked by H3K4me3 increases by more than one fifth; H3K27me3 undergoes dynamic genomic redistribution characterized by loss at half of gene promoters and overall reduction of peak size by almost one-half. This is paralleled by increased phosphorylation of EZH2 at serine 21. Among genes with highly altered mRNA expression, 23.1% switch between H3K4me3 and H3K27me3 marks, and those point to the master EMT targets and regulators CDH1, PDGFRA and ESRP1. Strikingly, Twist1 increases the number of bivalent genes by more than two fold. Inhibition of the H3K27 methyltransferases EZH2 and EZH1, which form part of the PRC2 complex, results in blocking EMT and stemness properties. Conclusion: Our findings demonstrate that the EMT program requires epigenetic remodeling by the Polycomb/Trithorax complexes leading to increased cellular plasticity which suggests that its inhibition will prevent EMT, and the associated breast cancer metastasis. ChIPseq profiles of human mammary epithelial cells before (HMLE_parental) and after Twist1 transfection (HMLE_Twist) were generated in monolayer (HMLE_Twist2D) and sphere culture by deep sequencing using Illumina GAIIx or Illumina hiseq2000 Please note that the processed data files were generated by pooling both replicate samples after confirming the high correlation of the two replicates.
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