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DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins

Journal Article · · Cell
 [1];  [2];  [3];  [1];  [3];  [3];  [3];  [3];  [4];  [4];  [3];  [5]
  1. Emory Univ. School of Medicine, Atlanta, GA (United States)
  2. National Inst. of Health (NIH), Bethesda, MD (United States); Tongji Univ., Shanghai (China)
  3. National Inst. of Health (NIH), Bethesda, MD (United States)
  4. The Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States)
  5. Emory Univ. School of Medicine, Atlanta, GA (United States); The Univ. of Texas MD Anderson Cancer Center, Houston, TX (United States)
Tandem zinc finger (ZF) proteins are the largest and most rapidly diverging family of DNA-binding transcription regulators in mammals. ZFP568 represses a transcript of placental-specific insulin like growth factor 2 (Igf2-P0) in mice. ZFP568 binds a 24-base pair sequence-specific element upstream of Igf2-P0 via the eleven-ZF array. Both DNA and protein conformations deviate from the conventional one finger-three bases recognition, with individual ZFs contacting 2, 3, or 4 bases and recognizing thymine on the opposite strand. These interactions arise from a shortened minor groove caused by an AT-rich stretch, suggesting adaptability of ZF arrays to sequence variations. Despite conservation in mammals, mutations at Igf2 and ZFP568 reduce their binding affinity in chimpanzee and humans. Furthermore, our studies provide important insights into the evolutionary and structural dynamics of ZF-DNA interactions that play a key role in mammalian development and evolution.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
NIH
OSTI ID:
1434722
Journal Information:
Cell, Journal Name: Cell Journal Issue: 1 Vol. 173; ISSN 0092-8674
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (4)

ZFP30 promotes adipogenesis through the KAP1-mediated activation of a retrotransposon-derived Pparg2 enhancer text January 2019
ZFP30 promotes adipogenesis through the KAP1-mediated activation of a retrotransposon-derived Pparg2 enhancer journal April 2019
Structural basis of specific DNA binding by the transcription factor ZBTB24 journal June 2019
ZFP30 promotes adipogenesis through the KAP1-mediated activation of a retrotransposon-derived Pparg2 enhancer. text January 2019

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