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DNA methylation regulates haematopoietic development

ABSTRACT: DNA methylation regulates haematopoietic development

PROVIDER: PRJNA703974 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13764220_1.fastq.gz	Fastqsanger.gz
	SRR13764220_2.fastq.gz	Fastqsanger.gz
	SRR13764221_1.fastq.gz	Fastqsanger.gz
	SRR13764221_2.fastq.gz	Fastqsanger.gz
	SRR13764222_1.fastq.gz	Fastqsanger.gz

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Maternal DNA methylation regulates early trophoblast development

Project description:Critical roles for DNA methylation in embryonic development are well established, but less is known about the roles of DNA methylation during trophoblast development, the extraembryonic lineage that gives rise to the placenta. Here we dissected the role of DNA methylation in trophoblast development by performing mRNA and DNA methylation profiling of Dnmt3a/3b-null trophoblast. We find that most gene deregulation is explained by an erasure of maternal methylation in the oocyte, but partially independent of loss of imprinting of the trophoblast-essential Ascl2 gene. Our results reveal that maternal DNA methylation controls multiple differentiation and physiological processes in trophoblast via both imprinting-dependent and -independent mechanisms. mRNA-seq and WGBS-seq of maternal Dnmt3a/3b-null trophoblast; mRNA-seq of maternal Ascl2 KO trophoblast

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DNA methylation in Vav-IDH1-KI mouse haematopoietic stem cells

Project description:Mutations in isocitrate dehydrogenase-1 (IDH1 R132) and -2 (IDH2 R140 and R172), which confer neomorphic enzymatic activity converting αKG (α-ketoglutarate) to D-2-hydroxyglutarate (D2HG), occur commonly in acute myeloid leukemia (AML). Mutant IDH1 alters epigenetics and increases haematopoietic progenitors in vivo, consistent with D2HG-mediated inhibition of TET2 5-methylcytosine hydroxylase. As TET2 mutations are mutually exclusive with IDH1/2 mutations and confer a similar phenotype, it has been widely believed that the oncogenicity of mutant IDH1/2 is due to TET2 inhibition. However, IDH1/2 mutations may have additional effects explaining the clinical features of MDS/MPN/AML. Here we show that mutant IDH1 downregulates ATM, thereby inhibiting DNA damage responses and increasing genomic instability. To investigate potential mechanisms of ATM downregulation, we examined ATM promoter DNA methylation in Vav-IDH1-KI long term haematopoietic stem cells (LT-HSC), short term haematopoietic stem cells (ST-HSC) and multipotent progenitors (MPP).

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Maternal DNA methylation regulates early trophoblast development

2016-01-07 | GSE66049 | GEO

DNA methylation regulates haematopoietic development

Project description:Focus on EHT and definitive hematopoiesis process including E10.0, E11.0, E14, Adult

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The adult haematopoietic stem cell CpG island methylome is almost entirely recapitulated in progeny cells: Implications for disease

Project description:Background Differences in immune response between individuals is driven in part by epigenetic factors. To understand the contribution of DNA methylation to these differences, we have investigated the role of haematopoietic stem cell methylation in driving variation in daughter cell differentiation and state. Methods Haematopoietic cells (namely CD34+, CD14+ and CD56+) were isolated from peripheral blood of 11 healthy individuals and subject to modified reduced representation bisulfite sequencing. DNA methylation was profiled and compared at CpG islands. Results DNA methylation state is almost entirely recapitulated between progenitor and progeny haematopoietic cells. Fewer differences in DNA methylation were detected between haematopoietic cells than between haematopoietic cells and buccal mucosa. Cell subset differences in methylation were over-represented near genes important in cell lineage specific maturation and function. Methylation differences between individuals at specific CpG islands were generally small. The CpG islands that varied most between individuals consistently across subsets, were associated with several genes, but were not enriched with regard to specific biological processes. Conclusions Overall, this study suggests that the predominant DNA methylation setting in haematopoietic stem cells is transmitted to progeny cells, with differences between cell subsets and between individuals that are likely to be important in immune cell development and variation in response to pathogens and disease. Our findings provide a plausible mechanism by which genetic and environmental factors may contribute to the development of disease via unfavourable DNA methylation settings.

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Project description:DNA methylation is a heritable chromatin modification essential to mammalian development that functions with histone post-translational modifications to regulate chromatin structure and gene expression programs. The epigenetic inheritance of DNA methylation requires the combined actions of DNMT1 and UHRF1, a histone- and DNA-binding RING E3 ubiquitin ligase that facilitates DNMT1 recruitment to sites of newly replicated DNA through the ubiquitylation of histone H3. UHRF1 binds DNA with modest selectivity towards hemi-methylated CpG dinucleotides (HeDNA); however, the contribution of HeDNA sensing to UHRF1 function remains elusive. Here, we reveal that the interaction of UHRF1 with HeDNA is required for DNA methylation inheritance but is dispensable for chromatin interaction, which is governed by reciprocal positive cooperativity between the UHRF1 histone- and DNA-binding domains. We further show that HeDNA functions as an allosteric regulator of UHRF1 ubiquitin ligase activity, directing ubiquitylation towards multiple lysines on the H3 tail adjacent to the UHRF1 histone-binding site. Collectively, our studies define a highly orchestrated epigenetic control mechanism involving modifications both to histones and DNA that facilitate UHRF1 chromatin targeting, H3 ubiquitylation, and DNA methylation inheritance.

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Valine-restricted diet regulates DNA methylation [Bisulfite-Seq]

Project description:Valine-restricted diet regulates DNA methylation [Bisulfite-Seq]

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Valine-restricted diet regulates DNA methylation [RNA-Seq]

Project description:Valine-restricted diet regulates DNA methylation [RNA-Seq]

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