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Crystal Structures of REF6 and Its Complex with DNA Reveal Diverse Recognition Mechanisms

51 Pages Posted: 24 Apr 2019 Sneak Peek Status: Review Complete

See all articles by Zizi Tian

Zizi Tian

China Agricultural University - State Key Laboratory of Agrobiotechnology

Xiaorong Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

Min Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

Wei Wu

China Agricultural University - State Key Laboratory of Agrobiotechnology

Manfeng Zhang

China Agricultural University - State Key Laboratory of Agrobiotechnology

Chenjun Tang

China Agricultural University - State Key Laboratory of Agrobiotechnology

Zhihui Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

Yunlong Liu

China Agricultural University - State Key Laboratory of Agrobiotechnology

Zhenhang Chen

China Agricultural University - State Key Laboratory of Agrobiotechnology

Meiting Yang

China Agricultural University - State Key Laboratory of Agrobiotechnology

Lulu Ma

China Agricultural University - State Key Laboratory of Agrobiotechnology

Cody Caba

University of Windsor - Department of Chemistry and Biochemistry

Yufeng Tong

University of Windsor - Department of Chemistry and Biochemistry

Hon-Ming Lam

The Chinese University of Hong Kong (CUHK) - State Key Laboratory of Agrobiotechnology

Zhongzhou Chen

China Agricultural University - State Key Laboratory of Agrobiotechnology

More...

Abstract

RELATIVE OF EARLY FLOWERING 6 (REF6) is a DNA-sequence-specific H3K27me3/2 demethylase containing four zinc finger (ZnF) domains, targeting several thousand genes in Arabidopsis thaliana. The ZnF domains are essential for binding target genes, but the structural basis and mechanisms remain unclear. Here, we determined crystal structures of the ZnF domains and its dsDNA complex. It is composed of a unique REF6-family-specific half-cross-braced ZnF (RCZ) domain and two C2H2-type ZnFs. DNA binding induces a profound conformational change of REF6 at the hinge region. Each REF6 recognizes six bases and DNA methylation reduces the binding affinity. Both the acidic region and basic region are crucial for the self-association of REF6. The binding ability and specificity are enhanced by combining base and shape readout, and cooperativity. The resulting conformational plasticity enables REF6 to function as a global transcriptional regulator that directly binds many diverse genes, revealing the structural basis of recognizing epigenetic modification.

Suggested Citation

Tian, Zizi and Li, Xiaorong and Li, Min and Wu, Wei and Zhang, Manfeng and Tang, Chenjun and Li, Zhihui and Liu, Yunlong and Chen, Zhenhang and Yang, Meiting and Ma, Lulu and Caba, Cody and Tong, Yufeng and Lam, Hon-Ming and Chen, Zhongzhou, Crystal Structures of REF6 and Its Complex with DNA Reveal Diverse Recognition Mechanisms (April 23, 2019). Available at SSRN: https://ssrn.com/abstract=3376664 or http://dx.doi.org/10.2139/ssrn.3376664
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Zizi Tian

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Xiaorong Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Min Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Wei Wu

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Manfeng Zhang

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Chenjun Tang

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Zhihui Li

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Yunlong Liu

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Zhenhang Chen

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Meiting Yang

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Lulu Ma

China Agricultural University - State Key Laboratory of Agrobiotechnology

China

Cody Caba

University of Windsor - Department of Chemistry and Biochemistry

Canada

Yufeng Tong

University of Windsor - Department of Chemistry and Biochemistry

Canada

Hon-Ming Lam

The Chinese University of Hong Kong (CUHK) - State Key Laboratory of Agrobiotechnology

Hong Kong

Zhongzhou Chen (Contact Author)

China Agricultural University - State Key Laboratory of Agrobiotechnology ( email )

China

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