ArticleThe Journal of biological chemistry2011
Transcription factors KLF1 and KLF2 positively regulate embryonic and fetal beta-globin genes through direct promoter binding.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.Blood · 2014Trial
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- Piezo1 accelerates osteoarthritis progression via promotion of HBB-dependent oxidative phosphorylation.The Journal of biological chemistry · 2026Article
- Mechanisms of Globin Gene Regulation in Mammals.Annual review of genetics · 2025Review
- Sex-biased transcriptome in in vitro produced bovine early embryos.Cell & bioscience · 2025Article
- The SWI/SNF-related protein SMARCA3 is a histone H3K23 ubiquitin ligase that regulates H3K9me3 in cancer.Molecular cell · 2025Article
- NSUN2 facilitates tenogenic differentiation of rat tendon-derived stem cells via m5C methylation of KLF2.Regenerative therapy · 2024Article
- Erythroid Krüppel-Like Factor (KLF1): A Surprisingly Versatile Regulator of Erythroid Differentiation.Advances in experimental medicine and biology · 2024Review
- Digits in a dish: AnFrontiers in cell and developmental biology · 2023Article
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- Mouse Models of Erythropoiesis and Associated Diseases.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Regulation of endothelial hemoglobin alpha expression by Kruppel-like factors.Vascular medicine (London, England) · 2017Article
- RNA sequencing analysis reveals protective role of kruppel-like factor 3 in colorectal cancer.Oncotarget · 2017Article
- Krüppel-like factors in mammalian stem cells and development.Development (Cambridge, England) · 2017Review
- ε-globin expression is regulated by SUV4-20h1.Haematologica · 2016Article
- Krüppel-Like Transcription Factor KLF1 Is Required for Optimal γ- and β-Globin Expression in Human Fetal Erythroblasts.PloS one · 2016Article
- The expression of embryonic globin mRNA in a severely anemic mouse model induced by treatment with nitrogen-containing bisphosphonate.BMC hematology · 2016Article
- GATA1 Activity Governed by Configurations ofFrontiers in oncology · 2016Review
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- The polycomb group protein L3MBTL1 represses a SMAD5-mediated hematopoietic transcriptional program in human pluripotent stem cells.Stem cell reports · 2015Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Krüppel-like factors (KLFs) control cell differentiation and embryonic development. KLF1 (erythroid Krüppel-like factor) plays essential roles in embryonic and adult erythropoiesis. KLF2 is a positive regulator of the mouse and human embryonic β-globin genes. KLF1 and KLF2 have highly homologous zinc finger DNA-binding domains. They have overlapping roles in embryonic erythropoiesis, as demonstrated using single and double KO mouse models. Ablation of the KLF1 or KLF2 gene causes embryonic lethality, but double KO embryos are more anemic and die sooner than either single KO. In this work, a dual human β-globin locus transgenic and KLF knockout mouse model was used. The results demonstrate that the human ε- (embryonic) and γ-globin (fetal) genes are positively regulated by KLF1 and KLF2 in embryos. Conditional KO mouse experiments indicate that the effect of KLF2 on embryonic globin gene regulation is at least partly erythroid cell-autonomous. KLF1 and KLF2 bind directly to the promoters of the human ε- and γ-globin genes, the mouse embryonic Ey- and βh1-globin genes, and also to the β-globin locus control region, as demonstrated by ChIP assays with mouse embryonic blood cells. H3K9Ac and H3K4me3 marks indicate open chromatin and active transcription, respectively. These marks are diminished at the Ey-, βh1-, ε- and γ-globin genes and locus control region in KLF1(-/-) embryos, correlating with reduced gene expression. Therefore, KLF1 and KLF2 positively regulate the embryonic and fetal β-globin genes through direct promoter binding. KLF1 is required for normal histone modifications in the β-globin locus in mouse embryos.
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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.