ArticleExperimental hematology2009
Developmentally regulated extended domains of DNA hypomethylation encompass highly transcribed genes of the human beta-globin locus.
Article in Experimental hematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Epigenetic and molecular profiles of erythroid cells after hydroxyurea treatment in sickle cell anemia.Blood · 2011Trial
- Mechanisms of establishment and functional significance of DNA demethylation during erythroid differentiation.Blood advances · 2018Article
- Long-term exposure of K562 cells to benzene metabolites inhibited erythroid differentiation and elevated methylation in erythroid specific genes.Toxicology research · 2016Article
- Transcriptional environment and chromatin architecture interplay dictates globin expression patterns of heterospecific hybrids derived from undifferentiated human embryonic stem cells or from their erythroid progeny.Experimental hematology · 2013Article
- Epigenetic modifications and chromosome conformations of the beta globin locus throughout development.Stem cell reviews and reports · 2013Article
- DNA methylation profiling of the fibrinogen gene landscape in human cells and during mouse and zebrafish development.PloS one · 2013Article
- Transcriptional signatures mediated by acetylation overlap with early-stage Alzheimer's disease.Experimental brain research · 2012Article
- Generation and characterization of erythroid cells from human embryonic stem cells and induced pluripotent stem cells: an overview.Stem cells international · 2011Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveDNA methylation has long been implicated in developmental beta-globin gene regulation. However, the mechanism underlying this regulation is unclear, especially because these genes do not contain CpG islands. This has led us to propose and test the hypothesis that, just as for histone modifications, developmentally specific changes in human beta-like globin gene expression are associated with long-range changes in DNA methylation. MATERIALS AND
methodsBisulfite sequencing was used to determine the methylation state of individual CpG dinucleotides across the beta-globin locus in uncultured primary human erythroblasts from fetal liver and bone marrow, and in primitive-like erythroid cells derived from human embryonic stem cells.
resultsbeta-globin locus CpGs are generally highly methylated, but domains of DNA hypomethylation spanning thousands of base pairs are established around the most highly expressed genes during each developmental stage. These large domains of DNA hypomethylation are found within domains of histone modifications associated with gene expression. We also find hypomethylation of a small proportion of gamma-globin promoters in adult erythroid cells, suggesting a mechanism by which adult erythroid cells produce fetal hemoglobin.
conclusionThis is one of the first reports to show that changes in DNA methylation patterns across large domains around non-CpG island genes correspond with changes in developmentally regulated histone modifications and gene expression. These data support a new model in which extended domains of DNA hypomethylation and active histone marks are coordinately established to achieve developmentally specific gene expression of non-CpG island genes.
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