DNA Conformation Induces Adaptable Binding by Tandem Zinc Finger Proteins

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2018 Mar 20

PMID 29551271

Citations 24

Authors

Anamika Patel

Peng Yang

Matthew Tinkham

Mihika Pradhan

Ming-An Sun

Yixuan Wang

Don Hoang

Gernot Wolf

John R Horton

Xing Zhang

Todd Macfarlan

Xiaodong Cheng

Affiliations

Soon will be listed here.

Abstract

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. 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.

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