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ICF-specific DNMT3B dysfunction interferes with intragenic regulation of mRNA transcription and alternative splicing (RRBS-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: GSE95745 | GEO | 2017/03/07

SECONDARY ACCESSION(S): PRJNA378322

REPOSITORIES: GEO

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

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2017-03-07 | GSE95746 | GEO

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

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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

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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

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knockin mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function.

2016-01-11 | E-GEOD-71039 | biostudies-arrayexpress

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

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

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