ArticleNucleic acids research2017
Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability.
Article in Nucleic acids research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Expanding the phenotypic spectrum associated with ZIC1 variants: A neurodevelopmental disorder with and without craniosynostosis.Genetics in medicine : official journal of the American College of Medical Genetics · 2026Article
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- ZNF33B facilitates Japanese encephalitis virus replication by controlling HSPB1/8-mediated SUMOylation of nonstructural protein 5.Journal of virology · 2025Article
- Predicting the DNA binding specificity of transcription factor mutants using family-level biophysically interpretable machine learning.Nucleic acids research · 2025Article
- NKX2-5 congenital heart disease mutations show diverse loss and gain of epigenomic, biochemical and chromatin search functions underpinning pathogenicity.bioRxiv : the preprint server for biology · 2025Article
- 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
- Missense mutations in CRX homeodomain cause dominant retinopathies through two distinct mechanisms.eLife · 2023Article
- Cooperative assembly confers regulatory specificity and long-term genetic circuit stability.Cell · 2023Article
- Pathogenic human variant that dislocates GATA2 zinc fingers disrupts hematopoietic gene expression and signaling networks.The Journal of clinical investigation · 2023Article
- EKLF/Klf1 regulates erythroid transcription by its pioneering activity and selective control of RNA Pol II pause-release.Cell reports · 2022Article
- Review
- Hemoglobin switching in mice carrying theHaematologica · 2021Article
- Transcriptional Control of Gene Expression and the Heterogeneous Cellular Identity of Erythroblastic Island Macrophages.Frontiers in genetics · 2021Review
- A new role of glutathione peroxidase 4 during human erythroblast enucleation.Blood advances · 2020Article
- KLF1/EKLF expression in acute leukemia is correlated with chromosomal abnormalities.Blood cells, molecules & diseases · 2020Article
- 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
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
The rules of engagement between zinc finger transcription factors and DNA have been partly defined by in vitro DNA-binding and structural studies, but less is known about how these rules apply in vivo. Here, we demonstrate how a missense mutation in the second zinc finger of Krüppel-like factor-1 (KLF1) leads to degenerate DNA-binding specificity in vivo, resulting in ectopic transcription and anemia in the Nan mouse model. We employed ChIP-seq and 4sU-RNA-seq to identify aberrant DNA-binding events genome wide and ectopic transcriptional consequences of this binding. We confirmed novel sequence specificity of the mutant recombinant zinc finger domain by performing biophysical measurements of in vitro DNA-binding affinity. Together, these results shed new light on the mechanisms by which missense mutations in DNA-binding domains of transcription factors can lead to autosomal dominant diseases.
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Registered trials
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