ArticleThe Journal of biological chemistry2013
High resolution methylome analysis reveals widespread functional hypomethylation during adult human erythropoiesis.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- HSC commitment-associated epigenetic signature is prognostic in acute myeloid leukemia.The Journal of clinical investigation · 2014Pooled it
- Disruption of methionine metabolism drives erythroid cell fate reprogramming by remodeling the H3K4me3 landscape.The Journal of clinical investigation · 2026Article
- DNMT1 regulates human erythropoiesis by modulating cell cycle and endoplasmic reticulum stress in a stage-specific manner.Cell death and differentiation · 2024Article
- Nucleated red blood cells explain most of the association between DNA methylation and gestational age.Communications biology · 2023Article
- The role of specialized cell cycles during erythroid lineage development: insights from single-cell RNA sequencing.International journal of hematology · 2022Review
- Epigenome-wide association study of bronchopulmonary dysplasia in preterm infants: results from the discovery-BPD program.Clinical epigenetics · 2022Article
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- Epigenetic regulation of pediatric and neonatal immune responses.Pediatric research · 2022Review
- Review
- Erythroid enucleation: a gateway into a "bloody" world.Experimental hematology · 2021Review
- Epigenetic modifiers in normal and aberrent erythropoeisis.Seminars in hematology · 2021Review
- HIF1α/TET1 Pathway Mediates Hypoxia-Induced Adipocytokine Promoter Hypomethylation in Human Adipocytes.Cells · 2020Article
- Cellular dynamics of mammalian red blood cell production in the erythroblastic island niche.Biophysical reviews · 2019Review
- Article
- Loss of Function of DOCK4 in Myelodysplastic Syndromes Stem Cells is Restored by Inhibitors of DOCK4 Signaling Networks.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- A Unique Epigenomic Landscape Defines Human Erythropoiesis.Cell reports · 2019Article
- Impact of ZBTB7A hypomethylation and expression patterns on treatment response to hydroxyurea.Human genomics · 2018Article
- Mechanisms of establishment and functional significance of DNA demethylation during erythroid differentiation.Blood advances · 2018Article
- Stage-specific differential DNA methylation data analysis during human erythropoiesis in chromosome 16.Genetics research · 2018Article
- Histone deacetylase 1 activates PU.1 gene transcription through regulating TAF9 deacetylation and transcription factor IID assembly.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
Corrections and comments
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Authors and funding
23 authors at 2 institutions in 1 country.
Funding
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.
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Registered trials
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