ArticleThe Journal of biological chemistry2009
EKLF/KLF1 controls cell cycle entry via direct regulation of E2f2.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 74 citations in OpenAlex.
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Erythropoiesis: insights from a genomic perspective.Experimental & molecular medicine · 2024Review
- Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis.Nature communications · 2024Article
- C2H2 Zinc Finger Transcription Factors Associated with Hemoglobinopathies.Journal of molecular biology · 2024Review
- Erythroid Krüppel-Like Factor (KLF1): A Surprisingly Versatile Regulator of Erythroid Differentiation.Advances in experimental medicine and biology · 2024Review
- RNA polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.Developmental cell · 2023Article
- Review
- RNA Polymerase II pausing temporally coordinates cell cycle progression and erythroid differentiation.medRxiv : the preprint server for health sciences · 2023Article
- Review
- The role of erythrocytes and erythroid progenitor cells in tumors.Open life sciences · 2022Review
- Erythroid enucleation: a gateway into a "bloody" world.Experimental hematology · 2021Review
- Hemoglobin switching in mice carrying theHaematologica · 2021Article
- Molecular Analysis of the E2F/DP Gene Family ofFrontiers in plant science · 2021Article
- Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages.Frontiers in genetics · 2021Review
- KLF1/EKLF expression in acute leukemia is correlated with chromosomal abnormalities.Blood cells, molecules & diseases · 2020Article
- AMolecular and cellular biology · 2020Article
- Corrupted DNA-binding specificity and ectopic transcription underpin dominant neomorphic mutations in KLF/SP transcription factors.BMC genomics · 2019Article
- Article
- The Pleiotropic Effects of GATA1 and KLF1 in Physiological Erythropoiesis and in Dyserythropoietic Disorders.Frontiers in physiology · 2019Review
- Survey and evaluation of mutations in the human KLF1 transcription unit.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Differentiation of erythroid cells requires precise control over the cell cycle to regulate the balance between cell proliferation and differentiation. The zinc finger transcription factor, erythroid Krüppel-like factor (EKLF/KLF1), is essential for proper erythroid cell differentiation and regulates many erythroid genes. Here we show that loss of EKLF leads to aberrant entry into S-phase of the cell cycle during both primitive and definitive erythropoiesis. This cell cycle defect was associated with a significant reduction in the expression levels of E2f2 and E2f4, key factors necessary for the induction of S-phase gene expression and erythropoiesis. We found and validated novel intronic enhancers in both the E2f2 and E2f4 genes, which contain conserved CACC, GATA, and E-BOX elements. The E2f2 enhancer was occupied by EKLF in vivo. Furthermore, we were able to partially restore cell cycle dynamics in EKLF(-/-) fetal liver upon additional genetic depletion of Rb, establishing a genetic causal link between reduced E2f2 and the EKLF cell cycle defect. Finally, we propose direct regulation of the E2f2 enhancer is a generic mechanism by which many KLFs regulate proliferation and differentiation.
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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.