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The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [microarray]

ABSTRACT: The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [microarray]

PROVIDER: PRJNA489188 | ENA |

REPOSITORIES: ENA

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The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [microarray]

Project description:Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the context of development and disease. DNA methylation by DNA methyltransferases (DNMTs) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell biological and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various DNMT-mutant mouse ES cell lines that include a line with a drug-inducible DNMT3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) correlates with redistribution of H3K27me3 induced upon DNA hypomethylation: later replicating PH coincides with H3K27me3 enriched regions. In contrast, this relationship with H3K27me3 was not evident at chromosomal arm regions that undergo either early-to-late (EtoL) or late-to-early (LtoE) replication timing switching upon loss of DNMTs. Interestingly, transcriptional up- and down-regulation frequently coincide with earlier and later shifts in replication timing of chromosomal arm regions, respectively. Our study revealed previously unrecognized complex and diverse roles of DNMTs in shaping the mammalian DNA replication landscape. We investigated the effect of Dnmt3a2 expression in the transcription profile of Dnmt3a and 3b double knockout (DKO) ES cells.

2021-02-12 | GSE119406 | GEO

The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication

Project description:The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication

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The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [BrdU-IP]

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The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [BrdU-IP]

Project description:The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication [BrdU-IP]

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The Temporal Order of DNA Replication Shaped by Mammalian DNA Methyltransferases.

Project description:Multiple epigenetic pathways underlie the temporal order of DNA replication (replication timing) in the contexts of development and disease. DNA methylation by DNA methyltransferases (Dnmts) and downstream chromatin reorganization and transcriptional changes are thought to impact DNA replication, yet this remains to be comprehensively tested. Using cell-based and genome-wide approaches to measure replication timing, we identified a number of genomic regions undergoing subtle but reproducible replication timing changes in various Dnmt-mutant mouse embryonic stem (ES) cell lines that included a cell line with a drug-inducible Dnmt3a2 expression system. Replication timing within pericentromeric heterochromatin (PH) was shown to be correlated with redistribution of H3K27me3 induced by DNA hypomethylation: Later replicating PH coincided with H3K27me3-enriched regions. In contrast, this relationship with H3K27me3 was not evident within chromosomal arm regions undergoing either early-to-late (EtoL) or late-to-early (LtoE) switching of replication timing upon loss of the Dnmts. Interestingly, Dnmt-sensitive transcriptional up- and downregulation frequently coincided with earlier and later shifts in replication timing of the chromosomal arm regions, respectively. Our study revealed the previously unrecognized complex and diverse effects of the Dnmts loss on the mammalian DNA replication landscape.

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The role of mammalian DNA methyltransferases in the regulation of temporal order of DNA replication

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

2021-02-12 | GSE119479 | GEO

Inhibition of uPA expression by CRISPR-dCas9 DNA methyltransferases

Project description:We report the generation of CRISPR-dCas9 DNA methyltransferases to mediate targeted DNA methylation. Using the dCas9-BFP-DNMT3A and dCas9-BFP-DNMT3B methyltransferases, we have demonstrated that these two methyltransferase can mediate targeted methylation in three human genes tested: uPA, TGFBR3, and CDKN2A in human HEK293T cells. We also showed that these methyltransferases could mediate gene inhibition. five samples co-transfected with five uPA sgRNAs and each of the four dCas9 fusions, or control transfection with pUC19 plasmid

2016-06-01 | E-GEOD-74935 | biostudies-arrayexpress

Inhibition of uPA expression by CRISPR-dCas9 DNA methyltransferases

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Cancer cells with genetic disruption of DNA methyltransferases

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DNA methyltransferases are complementary in maintaining DNA methylation in embryonic stem cells

Project description:To investigate the cooperative function DNMTs in the maintenance of DNA methylation at the ICRs, we established mutant ES clones lacking three major DNA methyltransferases (DNMTs).

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