ArticleProceedings of the National Academy of Sciences of the United States of America2006
Methyl binding domain protein 2 mediates gamma-globin gene silencing in adult human betaYAC transgenic mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 72 citations in OpenAlex.
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
- Removal of promoter CpG methylation by epigenome editing reverses HBG silencing.Nature communications · 2025Article
- The role of multivalency in the association of the eight twenty-one protein 2 (ETO2) with the nucleosome remodeling and deacetylase (NuRD) complex.Nucleic acids research · 2025Article
- The histone deacetylase inhibitor CT-101 flips the switch to fetal hemoglobin expression in sickle cell disease mice.PloS one · 2025Article
- Review
- MBD2a-NuRD binds to the methylated γ-globin gene promoter and uniquely forms a complex required for silencing of HbF expression.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Dual function NFI factors control fetal hemoglobin silencing in adult erythroid cells.Nature genetics · 2022Article
- Novel histone deacetylase inhibitor CT-101 induces γ-globin gene expression in sickle erythroid progenitors with targeted epigenetic effects.Blood cells, molecules & diseases · 2022Article
- CRISPR-Cas9 to induce fetal hemoglobin for the treatment of sickle cell disease.Molecular therapy. Methods & clinical development · 2021Review
- Exploring epigenetic and microRNA approaches for γ-globin gene regulation.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Epigenetic activities in erythroid cell gene regulation.Seminars in hematology · 2021Article
- The Methyl-CpG-Binding Domain 2 and 3 Proteins and Formation of the Nucleosome Remodeling and Deacetylase Complex.Journal of molecular biology · 2020Review
- Disruption of the MBD2-NuRD complex but not MBD3-NuRD induces high level HbF expression in human adult erythroid cells.Haematologica · 2019Article
- A new target for fetal hemoglobin reactivation.Haematologica · 2019Article
- Rational targeting of a NuRD subcomplex guided by comprehensive in situ mutagenesis.Nature genetics · 2019Article
- Readers of DNA methylation, the MBD family as potential therapeutic targets.Pharmacology & therapeutics · 2018Review
- Fetal haemoglobin induction in sickle cell disease.British journal of haematology · 2018Review
- Hypermethylated LTR retrotransposon exhibits enhancer activity.Epigenetics · 2017Article
- Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin.Science (New York, N.Y.) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The genes of the vertebrate beta-globin locus undergo a switch in expression during erythroid development whereby embryonic/fetal genes of the cluster are sequentially silenced and adult genes are activated. We describe here a role for DNA methylation and MBD2 in the silencing of the human fetal gamma-globin gene. The gamma-globin gene is reactivated upon treatment with the DNA methyltransferase inhibitor 5-azacytidine in the context of a mouse containing the entire human beta-globin locus as a yeast artificial chromosome (betaYAC) transgene. To elucidate the mechanism through which DNA methylation represses the gamma-globin gene in adult erythroid cells, betaYAC/MBD2-/- mice were generated by breeding betaYAC mice with MBD2-/- mice. Adult betaYAC/MBD2-/- mice continue to express the gamma-globin gene at a level commensurate with 5-azacytidine treatment, 10- to 20-fold over that observed with 1-acetyl-2-phenylhydrazine treatment alone. In addition, the level of gamma-globin expression is consistently higher in MBD2-/- mice in 14.5- and 16.5-days postcoitus fetal liver erythroblasts suggesting a role for MBD2 in embryonic/fetal erythroid development. DNA methylation levels are modestly decreased in MBD2-/- mice. MBD2 does not bind to the gamma-globin promoter region to maintain gamma-globin silencing. Finally, treatment of MBD2-null mice with 5-azacytidine induces only a small, nonadditive induction of gamma-globin mRNA, signifying that DNA methylation acts primarily through MBD2 to maintain gamma-globin suppression in adult erythroid cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.