Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (RIP-seq)

ABSTRACT: We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

ORGANISM(S): Homo sapiens

PROVIDER: GSE95744 | GEO | 2017/03/07

SECONDARY ACCESSION(S): PRJNA378323

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (RRBS-Seq)

Project description:We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing.

2017-03-07 | GSE95745 | GEO

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (RNA-seq)

2017-03-07 | GSE95743 | GEO

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (ChIP-Seq)

2017-03-07 | GSE95746 | GEO

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing

Project description:ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing

| PRJNA378257 | ENA

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing.

Project description:Hypomorphic mutations in DNA-methyltransferase DNMT3B cause majority of the rare disorder Immunodeficiency, Centromere instability and Facial anomalies syndrome cases (ICF1). By unspecified mechanisms, mutant-DNMT3B interferes with lymphoid-specific pathways resulting in immune response defects. Interestingly, recent findings report that DNMT3B shapes intragenic CpG-methylation of highly-transcribed genes. However, how the DNMT3B-dependent epigenetic network modulates transcription and whether ICF1-specific mutations impair this process remains unknown. We performed a transcriptomic and epigenomic study in patient-derived B-cell lines to investigate the genome-scale effects of DNMT3B dysfunction. We highlighted that altered intragenic CpG-methylation impairs multiple aspects of transcriptional regulation, like alternative TSS usage, antisense transcription and exon splicing. These defects preferentially associate with changes of intragenic H3K4me3 and at lesser extent of H3K27me3 and H3K36me3. In addition, we highlighted a novel DNMT3B activity in modulating the self-regulatory circuit of sense-antisense pairs and the exon skipping during alternative splicing, through interacting with RNA molecules. Strikingly, altered transcription affects disease relevant genes, as for instance the memory-B cell marker CD27 and PTPRC genes, providing us with biological insights into the ICF1-syndrome pathogenesis. Our genome-scale approach sheds light on the mechanisms still poorly understood of the intragenic function of DNMT3B and DNA methylation in gene expression regulation.

| S-EPMC5449610 | biostudies-literature

ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-03-07 | GSE95747 | GEO

DNA methyltransferase 3B (DNMT3B) mutations in ICF syndrome: gene expression analysis

Project description:Genome-wide DNA methylation patterns are established and maintained by the coordinated action of three DNA methyltransferases, DNMT1, DNMT3A, and DNMT3B. DNMT3B hypomorphic germline mutations are responsible for two-thirds of Immunodeficiency, Centromere Instability, Facial Anomalies (ICF) syndrome cases. The molecular defects in transcription, DNA methylation, and chromatin structure in ICF cells remain relatively uncharacterized. We used expressing microarrays to define the global program of gene expression to elucidate the role of DNMT3B in these processes using EBV-immortalized lymphoblastoid cell lines (LCLs) derived from ICF syndrome and normal individuals. Keywords: disease-state analysis

2007-11-01 | GSE9499 | GEO

Intragenic DNA methylation prevents cryptic transcription initiations on gene bodies [CAPIP-seq]

Project description:In mammals, DNA methylation occurs mainly at 5mC of CpG dinucleotides. The methylation on the promoter leads to the suppression of gene expression, while the functional role of gene body DNA methylation in highly expressed genes has yet to be clarified. Here, we show that the Dnmt3b-dependent intragenic DNA methylation protects the gene body from RNA Polymerase II (RNA Pol II) spurious entry and cryptic transcription initiation. Using different genome-wide approaches, we demonstrate that loss of Dnmt3b leads to an increase of the RNA Pol II engagement within gene bodies and spurious intragenic transcription initiation events. Furthermore, inhibition of RNA Pol II spurious entry depends on the enzymatic activity of the Dnmt3b recruited by H3K36me3. Thus, elongating RNA Pol II triggers an epigenetic crosstalk that involves SetD2, H3K36me3, Dnmt3b, and DNA methylation to ensure gene transcription initiation fidelity with implications for intragenic hypomethylation in cancer.

2017-02-25 | GSE72852 | GEO

Intragenic DNA methylation prevents cryptic transcription initiations on gene bodies [ART-seq]

2017-02-25 | GSE72851 | GEO

Intragenic DNA methylation prevents cryptic transcription initiations on gene bodies [BS-seq]

2017-02-25 | GSE72850 | GEO