ArticleNucleic acids research2018
Mbd2-CP2c loop drives adult-type globin gene expression and definitive erythropoiesis.
Article in Nucleic acids research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Spatiotemporal expression and control of haemoglobin in space.Nature communications · 2024Article
- A Cell-Penetrant Peptide Disrupting the Transcription Factor CP2c Complexes Induces Cancer-Specific Synthetic Lethality.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Structural and Functional Insights into CP2c Transcription Factor Complexes.International journal of molecular sciences · 2022Article
- p66α Suppresses Breast Cancer Cell Growth and Migration by Acting as Co-Activator of p53.Cells · 2021Article
- YY1 and CP2c in Unidirectional Spermatogenesis and Stemness.Development & reproduction · 2020Review
- Regulating the Regulators: The Role of Histone Deacetylase 1 (HDAC1) in Erythropoiesis.International journal of molecular sciences · 2020Review
- Article
- Rational discovery of antimetastatic agents targeting the intrinsically disordered region of MBD2.Science advances · 2019Article
- Article
- Potential new approaches to the management of the Hb Bart's hydrops fetalis syndrome: the most severe form of α-thalassemia.Hematology. American Society of Hematology. Education Program · 2018Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During hematopoiesis, red blood cells originate from the hematopoietic stem cell reservoir. Although the regulation of erythropoiesis and globin expression has been intensively investigated, the underlining mechanisms are not fully understood, including the interplay between transcription factors and epigenetic factors. Here, we uncover that the Mbd2-free NuRD chromatin remodeling complex potentiates erythroid differentiation of proerythroblasts via managing functions of the CP2c complexes. We found that both Mbd2 and Mbd3 expression is downregulated during differentiation of MEL cells in vitro and in normal erythropoiesis in mouse bone marrow, and Mbd2 downregulation is crucial for erythropoiesis. In uninduced MEL cells, the Mbd2-NuRD complex is recruited to the promoter via Gata1/Fog1, and, via direct binding through p66α, it acts as a transcriptional inhibitor of the CP2c complexes, preventing their DNA binding and promoting degradation of the CP2c family proteins to suppress globin gene expression. Conversely, during erythropoiesis in vitro and in vivo, the Mbd2-free NuRD does not dissociate from the chromatin and acts as a transcriptional coactivator aiding the recruitment of the CP2c complexes to chromatin, and thereby leading to the induction of the active hemoglobin synthesis and erythroid differentiation. Our study highlights the regulation of erythroid differentiation by the Mbd2-CP2c loop.
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