ArticleProceedings of the National Academy of Sciences of the United States of America2010
Severe anemia in the Nan mutant mouse caused by sequence-selective disruption of erythroid Kruppel-like factor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 76 citations in OpenAlex.
- Hereditary disorders of ineffective erythropoiesis.Blood cells, molecules & diseases · 2025Review
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Mutations in linker-2 of KLF1 impair expression of membrane transporters and cytoskeletal proteins causing hemolysis.Nature communications · 2024Article
- Erythroid Krüppel-Like Factor (KLF1): A Surprisingly Versatile Regulator of Erythroid Differentiation.Advances in experimental medicine and biology · 2024Review
- Schistosoma japonicum EKLF/KLF1 is a potential immune target to tackle schistosomiasis.Parasites & vectors · 2023Article
- Mammalian life depends on two distinct pathways of DNA damage tolerance.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Modelling the erythroblastic island niche of dyserythropoietic anaemia type IV patients using induced pluripotent stem cells.Frontiers in cell and developmental biology · 2023Article
- EKLF/Klf1 regulates erythroid transcription by its pioneering activity and selective control of RNA Pol II pause-release.Cell reports · 2022Article
- Review
- Epigenetic and Transcriptional Control of Erythropoiesis.Frontiers in genetics · 2022Review
- Hemoglobin switching in mice carrying theHaematologica · 2021Article
- AMolecular and cellular biology · 2020Article
- Genetic disarray follows mutant KLF1-E325K expression in a congenital dyserythropoietic anemia patient.Haematologica · 2019Article
- 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
- Detecting and interpreting DNA methylation marks.Current opinion in structural biology · 2018Review
- Mutant KLF1 in Adult Anemic Nan Mice Leads to Profound Transcriptome Changes and Disordered Erythropoiesis.Scientific reports · 2018Article
- Survey and evaluation of mutations in the human KLF1 transcription unit.Scientific reports · 2018Article
- Thyroid hormone receptor beta and NCOA4 regulate terminal erythrocyte differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Studies of mouse models of anemia have long provided fundamental insights into red blood cell formation and function. Here we show that the semidominant mouse mutation Nan ("neonatal anemia") carries a single amino acid change (E339D) within the second zinc finger of the erythroid Krüppel-like factor (EKLF), a critical erythroid regulatory transcription factor. The mutation alters the DNA-binding specificity of EKLF so that it no longer binds promoters of a subset of its DNA targets. Remarkably, even when mutant Nan and wild-type EKLF alleles are expressed at equivalent levels, the mutant form selectively interferes with expression of EKLF target genes whose promoter elements it no longer binds. This interference yields a distorted genetic output and selective protein deficiencies that differ from those seen in EKLF-heterozygous and EKLF-null red blood cells and presents a unique and unexpected mechanism of inherited disease.
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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.