ArticleMolecular and cellular biology2011
Nuclear receptors TR2 and TR4 recruit multiple epigenetic transcriptional corepressors that associate specifically with the embryonic β-type globin promoters in differentiated adult erythroid cells.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 110 citations in OpenAlex.
- Oral tetrahydrouridine and decitabine for non-cytotoxic epigenetic gene regulation in sickle cell disease: A randomized phase 1 study.PLoS medicine · 2017Trial
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Comprehensive regulation of γ-globin expression by epigenetic modifications and protein post-translational modifications.Clinical epigenetics · 2025Review
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- Orphan Nuclear Receptors TR2 and TR4 in Erythropoiesis: From Mechanisms to Therapies.Biomolecules · 2025Review
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- Genetic Modifiers of Hemoglobin Expression from a Clinical Perspective in Hemoglobinopathy Patients with Beta Thalassemia and Sickle Cell Disease.International journal of molecular sciences · 2024Review
- Review
- PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease.Science advances · 2024Article
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- LSD1 promotes the egress of hematopoietic stem and progenitor cells into the bloodstream during the endothelial-to-hematopoietic transition.Developmental biology · 2023Article
- Five nucleotides found in RCTG motifs are essential for post-fertilization methylation imprinting of the H19 ICR in YAC transgenic mice.Nucleic acids research · 2023Article
- Combinatorial targeting of epigenome-modifying enzymes with decitabine and RN-1 synergistically increases HbF.Blood advances · 2023Article
- Review
- Effect of the LSD1 inhibitor RN-1 on γ-globin and global gene expression during erythroid differentiation in baboons (Papio anubis).PloS one · 2023Article
- Generation of TRIM28 Knockout K562 Cells by CRISPR/Cas9 Genome Editing and Characterization of TRIM28-Regulated Gene Expression in Cell Proliferation and Hemoglobin Beta Subunits.International journal of molecular sciences · 2022Article
- Down-regulation of the transcriptional repressor ZNF802 (JAZF1) reactivates fetal hemoglobin in βScientific reports · 2022Article
- Lysine-specific histone demethylase 1 inhibition enhances robust fetal hemoglobin induction in human βHematology reports · 2021Article
- Transcriptional silencing of fetal hemoglobin expression by NonO.Nucleic acids research · 2021Article
- The Role of Histone Deacetylase 3 Complex in Nuclear Hormone Receptor Action.International journal of molecular sciences · 2021Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Nuclear receptors TR2 and TR4 (TR2/TR4) were previously shown to bind in vitro to direct repeat elements in the mouse and human embryonic and fetal β-type globin gene promoters and to play critical roles in the silencing of these genes. By chromatin immunoprecipitation (ChIP) we show that, in adult erythroid cells, TR2/TR4 bind to the embryonic β-type globin promoters but not to the adult β-globin promoter. We purified protein complexes containing biotin-tagged TR2/TR4 from adult erythroid cells and identified DNMT1, NuRD, and LSD1/CoREST repressor complexes, as well as HDAC3 and TIF1β, all known to confer epigenetic gene silencing, as potential corepressors of TR2/TR4. Coimmunoprecipitation assays of endogenous abundance proteins indicated that TR2/TR4 complexes consist of at least four distinct molecular species. In ChIP assays we found that, in undifferentiated murine adult erythroid cells, many of these corepressors associate with both the embryonic and the adult β-type globin promoters but, upon terminal differentiation, they specifically dissociate only from the adult β-globin promoter concomitant with its activation but remain bound to the silenced embryonic globin gene promoters. These data suggest that TR2/TR4 recruit an array of transcriptional corepressors to elicit adult stage-specific silencing of the embryonic β-type globin genes through coordinated epigenetic chromatin modifications.
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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.