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Unknown,Transcriptomics,Genomics,Proteomics

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Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a [Bisulfite-Seq]

ABSTRACT: Gains and losses in DNA methylation are prominent genomic features of all mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation patterns and thus contribute to cell fate, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine in purified wild type and Dnmt3a conditional knockout hematopoietic stem cells (HSCs). We generated 1,121 million (control HSCs), and 1,213 million (Dnmt3a knockout HSCs) raw reads; about 81.4% and 88.7%, respectively, were successfully aligned to either strand of the reference genome (mm9), obtainig an average CG coverage of 39.5-fold (wild type) and 47.0-fold (Dnmt3a kockout). Whole genome bisulfite sequencing of secondarily-transplanted wild-type and Dnmt3a conditional knockout hematopoietic stem cells using Illumina HiSeq 2000

ORGANISM(S): Mus musculus

SUBMITTER: Margaret Goodell

PROVIDER: E-GEOD-49714 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a (CMS bisulfite-seq)

Project description:Gains and losses in DNA methylation are prominent genomic features of all mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA 5-hydroxymethylation (5hmc) patterns and thus contribute to cell fate, including malignant transformation, we performed genome-wide mapping of 5hmc in purified wild type and Dnmt3a conditional knockout hematopoietic stem cells (HSCs) using cytosine-5-methylenesulphonate sequencing (CMS-seq). Comparing anti-CMS pulldown to input control, we identified 107,549 and 175,682 peaks of 5hmc enrichment in control and Dnmt3a knockout HSCs, respectively. Whole genome CMS-enriched bisulfite sequencing of secondarily-transplanted wild-type and Dnmt3a conditional knockout hematopoietic stem cells using Illumina HiSeq 2000

2014-01-22 | E-GEOD-53742 | biostudies-arrayexpress

Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a [Bisulfite-Seq]

Project description:Gains and losses in DNA methylation are prominent genomic features of all mammalian cell types. To gain insight into mechanisms that could promote shifts in DNA methylation patterns and thus contribute to cell fate, including malignant transformation, we performed genome-wide mapping of 5-methylcytosine in purified wild type and Dnmt3a conditional knockout hematopoietic stem cells (HSCs). We generated 1,121 million (control HSCs), and 1,213 million (Dnmt3a knockout HSCs) raw reads; about 81.4% and 88.7%, respectively, were successfully aligned to either strand of the reference genome (mm9), obtainig an average CG coverage of 39.5-fold (wild type) and 47.0-fold (Dnmt3a kockout).

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Aspartyl-tRNA synthetase 2 orchestrates iron-sulfur metabolism in hematopoietic stem cells via fine-tuning alternative RNA splicing

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2023-09-26 | PXD045562 | Pride

DNMT3A clonal hematopoiesis-driver mutations induce cardiac fibrosis by paracrine activation of fibroblasts

Project description:Hematopoietic mutations in epigenetic regulators like DNA methyltransferase 3 alpha (DNMT3A) drive clonal hematopoiesis of indeterminate potential (CHIP) and are associated with adverse prognosis in patients with heart failure (HF). The interactions between CHIP-mutated cells and other cardiac cell types remain unknown. Here, we identify fibroblasts as potential interaction partners of CHIP-mutated monocytes using combined transcriptomic data from peripheral blood mononuclear cells of HF patients with and without CHIP and cardiac tissue. We demonstrate that DNMT3A inactivation augments macrophage-to-cardiac fibroblasts interactions and induces cardiac fibrosis in mice and humans. Mechanistically, DNMT3A inactivation increases the release of heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) to activate cardiac fibroblasts. These findings not only identify a novel pathway of DNMT3A CHIP-driver mutation-induced instigation and progression of HF, but may also provide a rationale for the development of new anti-fibrotic strategies.

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Expression data from control and LRF (leukemia/lymphoma related factor)-deficient mouse LT-HSCs

Project description:LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis. We performed gene expression microarray analysis of FACS-sorted LT-HSCs (LSK IL7Ra-Flt3-CD150+CD48-) to assess the effect of Lrf loss on the LT-HSC transcriptome. Zbtb7a Flox/+ Mx1-Cre+ mice were used as a control to normalize the potential effects of Cre recombinase. LT-HSCs were FACS-sorted from three Lrf knockout (Zbtb7a Flox/Flox Mx1-Cre+) and two control (Zbtb7a Flox/+ Mx1-Cre+) mice, nine days after the first pIpC injection.

2012-10-26 | E-GEOD-41839 | biostudies-arrayexpress

de novo DNA Methylation Balances Hematopoietic Stem Cell Self-Renewal and Differentiation

Project description:Cytosine methylation is an epigenetic mark usually associated with gene repression. Despite a requirement for de novo DNA methylation for differentiation of embryonic stem cells, its role in somatic stem cells is unknown. Using conditional ablation, we show that loss of either, or both, Dnmt3a or Dnmt3b, progressively impedes hematopoietic stem cell (HSC) differentiation during serial in vivo passage. Concomitantly, HSC self-renewal is immensely augmented in absence of either Dnmt3, particularly Dnmt3a. Dnmt3-KO HSCs show upregulation of HSC multipotency genes and downregulation of early differentiation factors, and the differentiated progeny of Dnmt3-KO HSCs exhibit hypomethylation and incomplete repression of HSC-specific genes. HSCs lacking Dnmt3a manifest hyper-methylation of CpG islands and hypo-methylation of genes which are highly correlated with human hematologic malignancies. These data establish that aberrant DNA methylation has direct pathologic consequences for somatic stem cell development, leading to inefficient differentiation and maintenance of a self-renewal program. Reduced representation bisulfite sequencing (MspI,~40-220bp size fraction) of secondarily-transplanted wild-type and Dnmt3a conditional knockout hematopoietic stem cells. We used microarrays to detail the global expression of genes in secondarily-transplanted control-HSCs and Dnmt3a-KO-HSCs.

2011-09-30 | E-GEOD-27322 | biostudies-arrayexpress

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Project description:Meis1 encodes a TALE family homeodomain protein that was first identified as a common retroviral integration site in mouse BHX2 myeloid leukemia. It functions as a DNA binding co-factor of Hox proteins through interacting with Pbx, a member of another TALE family protein. Moreover, Meis1 homozygous knockout mice are embryonic lethal, showing significant defects in vasculogenesis, eye development and hematopoiesis. Severe defects were also observed in adult hematopoiesis by conditional inactivation of Meis1 in vivo. Meis1 is critical to maintain the balance between enter and exit from cell cycles of hematopoietic stem cells (HSCs), indicating that Meis1 regulates self-renewal and quiescence of HSCs. Total RNA was isolated from KSL cells obtained from poly(I:C)-treated Mx1-Cre Meis1fl/fl and sham-treated Meis1fl/fl mice.

2013-12-01 | E-GEOD-38336 | biostudies-arrayexpress

Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a (CMS bisulfite-seq)

2014-01-22 | GSE53742 | GEO

Large conserved domains of low DNA methylation maintained by 5-hydroxymethycytosine and Dnmt3a

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-11-16 | E-GEOD-49191 | biostudies-arrayexpress

Next Generation Sequencing Facilitates Quantitative Analysis of peritoneal macrophages Transcriptomes of Dnmt3a macrophage conditional knockout mouse

Project description:Purpose:The purpose of this study is to measure the gene expression profile in Dnmt3a conditional knockout macrophages. Methods:Dnmt3a conditional knockout macrophages mRNA profiles were generated by deep sequencing,using Illumina. Results: We mapped about 20 million sequence reads per sample to the mouse genome, identified hundreds of genes with significant mRNA variation during Dnmt3a conditional knockout in macrophages. Dnmt3a conditional knockout mRNA profiles were generated by deep sequencing

2016-05-30 | E-GEOD-74750 | biostudies-arrayexpress

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