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Mus musculus

ABSTRACT: Quantitative analysis of WT, Dnmt3a-/-, Dnmt3b-/- and Tet1-/- J1 ES cell transcriptomes

PROVIDER: PRJNA393526 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5812870_1.fastq.gz	Fastqsanger.gz
	SRR5812870_2.fastq.gz	Fastqsanger.gz
	SRR5812871_1.fastq.gz	Fastqsanger.gz
	SRR5812871_2.fastq.gz	Fastqsanger.gz
	SRR5812864_1.fastq.gz	Fastqsanger.gz

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Project description:Genome-wide maps of Dnmt3a1 binding in WT and Tet1-/- J1 ES cells

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Genome-wide maps of Tet1 binding in [WT, Tet1-Flag] and [Dnmt3a-/-, Tet1-Flag] J1 ES cells

Project description:In order to assess Tet1 binding, we first generated a Flag tagged Tet1 ES cells and then knocked out Dnmt3a in the [WT, Tet1-Flag] cells. By Tet1 ChIP and Flag ChIP, we showed that Tet1 binding was complementary to Dnmt3a. And Tet1 binding was not affected or slightly increased at majority of its targets.

2018-05-16 | GSE100955 | GEO

Genome-wide maps of histone modifications (SpikeIn) and Suz12 in WT, Dnmt3a-/-, Tet1-/- J1 and DKO ES cells.

Project description:Genome-wide maps of histone modifications (SpikeIn) and Suz12 in WT, Dnmt3a-/-, Tet1-/- J1 and DKO ES cells.

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Genome-wide identification of distinct target loci for de novo DNA methylation by DNMT3A and DNMT3B during mammalian development

Project description:DNA methylation plays essential roles in mammalian development. During post-implantation development, de novo establishment of DNA methylation is accomplished by DNA methyltransferases, in particular DNMT3A and DNMT3B. At present, the distinct functions of these two enzymes remain largely elusive. To comprehensively identify the target sites for de novo DNA methylation by the DNMT3 enzymes, we took advantage of female mouse ES cells established in the presence of MEK and Gsk3 inhibitors, which lack most DNA methylation (2i/L ES cells), in combination with genetic ablation of Dnmt3a or Dnmt3b. We analyzed de novo DNA methylation in mouse embryonic fibroblasts (2i-MEFs) derived from Dnmt3 knockout (KO) 2i/L ES cells. Both Dnmt3a and Dnmt3b KO 2i-MEFs exhibited a modest but global reduction in CpG methylation, which was particularly notable on the X chromosome in Dnmt3b KO cells. Although most genes were methylated similarly in both knockouts, we identified 355 and 333 uniquely unmethylated genes in Dnmt3a and Dnmt3b KO 2i-MEFs, respectively. Notably, Dnmt3a was exclusively required for de novo methylation at both TSS regions and gene bodies of Polycomb group (PcG) target developmental genes. Consistent with this, tissue-specific DNA methylation at PcG target developmental genes was substantially reduced in Dnmt3a KO embryos. Finally, we found that human patients with DNMT3A mutant acute myeloid leukemia (AML) or harboring DNMT3B mutation associated with immunodeficiency, centromere, and facial anomalies (ICF) syndrome exhibited reduced CpG methylation at regions that were hypomethylated in Dnmt3a or Dnmt3b KO 2i-MEFs, respectively. Collectively, our findings in DNA-hypomethylated 2i/L ES cells revealed a set of unique de novo DNA methylation target sites for both DNMT3 enzymes during mammalian development that overlap with hypomethylated sites in human patients.

2020-05-13 | GSE111172 | GEO

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