Dataset Information

High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis.

ABSTRACT: Differentiation of hematopoietic stem cells to red cells requires coordinated expression of numerous erythroid genes and is characterized by nuclear condensation and extrusion during terminal development. To understand the regulatory mechanisms governing these widespread phenotypic changes, we conducted a high resolution methylomic and transcriptomic analysis of six major stages of human erythroid differentiation. We observed widespread epigenetic differences between early and late stages of erythropoiesis with progressive loss of methylation being the dominant change during differentiation. Gene bodies, intergenic regions, and CpG shores were preferentially demethylated during erythropoiesis. Epigenetic changes at transcription factor binding sites correlated significantly with changes in gene expression and were enriched for binding motifs for SCL, MYB, GATA, and other factors not previously implicated in erythropoiesis. Demethylation at gene promoters was associated with increased expression of genes, whereas epigenetic changes at gene bodies correlated inversely with gene expression. Important gene networks encoding erythrocyte membrane proteins, surface receptors, and heme synthesis proteins were found to be regulated by DNA methylation. Furthermore, integrative analysis enabled us to identify novel, potential regulatory areas of the genome as evident by epigenetic changes in a predicted PU.1 binding site in intron 1 of the GATA1 gene. This intronic site was found to be conserved across species and was validated to be a novel PU.1 binding site by quantitative ChIP in erythroid cells. Altogether, our study provides a comprehensive analysis of methylomic and transcriptomic changes during erythroid differentiation and demonstrates that human terminal erythropoiesis is surprisingly associated with hypomethylation of the genome.

SUBMITTER: Yu Y

PROVIDER: S-EPMC3610956 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis.

Yu Yiting Y Mo Yongkai Y Ebenezer David D Bhattacharyya Sanchari S Liu Hui H Sundaravel Sriram S Giricz Orsolya O Wontakal Sandeep S Cartier Jessy J Caces Bennett B Artz Andrew A Nischal Sangeeta S Bhagat Tushar T Bathon Kathleen K Maqbool Shahina S Gligich Oleg O Suzuki Masako M Steidl Ulrich U Godley Lucy L Skoultchi Art A Greally John J Wickrema Amittha A Verma Amit A

The Journal of biological chemistry 20130110 13

Differentiation of hematopoietic stem cells to red cells requires coordinated expression of numerous erythroid genes and is characterized by nuclear condensation and extrusion during terminal development. To understand the regulatory mechanisms governing these widespread phenotypic changes, we conducted a high resolution methylomic and transcriptomic analysis of six major stages of human erythroid differentiation. We observed widespread epigenetic differences between early and late stages of ery ...[more]

PMID: 23306203

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Project description:Differentiation of hematopoietic stem cells to red cells requires coordinated expression of numerous erythroid genes. To understand the regulatory mechanisms governing lineage commitment we conducted a high resolution methylomic and transcriptomic analysis of six major stages of human erythroid differentiation. We observed widespread epigenetic differences between early and late stages of erythropoiesis with progressive loss of methylation being the dominant change during differentiation. Gene bodies, intergenic regions and CpG shores were preferentially demethylated during erythropoiesis. Epigenetic changes at transcription factor binding sites correlated significantly with changes in gene expression and were enriched for binding motifs for SCL, MYB, GATA and other factors not previously implicated in erythropoiesis. Demethylation at gene promoters was associated with increased expression of genes, while epigenetic changes at gene bodies correlated inversely with gene expression. Important gene networks encoding erythrocyte membrane proteins, surface receptors and heme synthesis proteins were found to be regulated by DNA methylation. Furthermore, integrative analysis enabled us to identify novel, potential regulatory areas of the genome that underwent differential methylation and correlated with corresponding changes in gene expression, as evident by epigenetic changes in a predicted PU.1 binding site in intron 1 of the GATA1 gene. This intronic site was found to be conserved across species and was validated to be a novel PU.1 binding site by qCHIP in erythroid cells. Altogether, our study provides a comprehensive analysis of methylomic and transcriptomic changes during erythroid differentiation and demonstrates that hypomethylation of the genome during erythroid differentiation has implications in modulating gene expression. We examined changes in methylation on days 0, 3, 7, 10, 13 and 16 of human erythroid culture. Two independent sets of experiments were performed.

Project description:BackgroundContinuous cropping stress involves such factors as biological barriers, allelopathic autotoxicity, deterioration of soil physicochemical properties, and soil fertility imbalance and is regarded as a kind of comprehensive stress limiting soybean yield and quality. Genomic DNA methylation is an important regulatory mechanism for plants to resist various environmental stresses. Therefore, it is especially worthwhile to reveal genomic methylation characteristics under stress and clarify the relationship between DNA methylation status and continuous cropping stress adaptability in soybean.ResultsWe generated a genome-wide map of cytosine methylation induced by this kind of comprehensive stress in a tolerant soybean variety (Kang Xian 2, KX2) and a sensitive variety (He Feng, HF55) using whole-genome bisulfite sequencing (WGBS) technology. The expression of DNA demethylase genes was detected using real-time quantitative PCR (qRT-PCR). The functions of differentially methylated genes (DMGs) involved in stress response in biochemical metabolism and genetic information transmission were further assessed based on Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The results showed that genomic DNA demethylation was closely related to continuous cropping comprehensive stress adaptability in soybean, which was further verified by the increasing expression of DNA demethylases ROS1 and DML. The demethylation of mCpG and mCpHpG (mCpApG preferred) contexts was more critical, which mainly occurred in gene-regulatory regions at the whole-chromosome scale. Moreover, this kind of stress adaptability may be related to various stress responders generated through strengthened glucose catabolism and amino acid and fatty acid anabolism, as well as fidelity transmission of genetic information.ConclusionsGenomic DNA demethylation was closely associated with continuous cropping comprehensive stress adaptability, highlighting the promising potential of screening continuous cropping-tolerant cultivars by DNA methylation index and further exploring the application of DNA demethylases in soybean breeding.

Dataset Information

High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis.

Publications

High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis.

Similar Datasets

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