Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability

@inproceedings{Gillinder2016PromiscuousDO,
  title={Promiscuous DNA-binding of a mutant zinc finger protein corrupts the transcriptome and diminishes cell viability},
  author={Kevin R Gillinder and Melissa D Ilsley and Danitza N{\'e}bor and Ravi Sachidanandam and Mathieu Lajoie and Graham W. Magor and Michael R. Tallack and Timothy L. Bailey and Michael John Landsberg and Joel P. Mackay and Michael W Parker and Luke A. Miles and Joel H. Graber and Luanne Laurel Peters and James J Bieker and Andrew C. Perkins},
  booktitle={Nucleic acids research},
  year={2016}
}
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… CONTINUE READING