Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2

Ting Zhou; Jun Xiong; Mingzhu Wang; Na Yang; Jiemin Wong; Bing Zhu; Rui Ming Xu

doi:10.1016/j.molcel.2014.04.003

Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2

Ting Zhou
, Jun Xiong
, Mingzhu Wang
, Na Yang
, Jiemin Wong
, Bing Zhu
, Rui Ming Xu^*

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

99 Scopus citations

Abstract

Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

Original language	English
Pages (from-to)	879-886
Number of pages	8
Journal	Molecular Cell
Volume	54
Issue number	5
DOIs	https://doi.org/10.1016/j.molcel.2014.04.003
State	Published - 5 Jun 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.molcel.2014.04.003

Cite this

@article{aa619dc3861a44a4933dc90ac2a8ad16,

title = "Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2",

abstract = "Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.",

author = "Ting Zhou and Jun Xiong and Mingzhu Wang and Na Yang and Jiemin Wong and Bing Zhu and Xu, \{Rui Ming\}",

year = "2014",

month = jun,

day = "5",

doi = "10.1016/j.molcel.2014.04.003",

language = "英语",

volume = "54",

pages = "879--886",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2

AU - Zhou, Ting

AU - Xiong, Jun

AU - Wang, Mingzhu

AU - Yang, Na

AU - Wong, Jiemin

AU - Zhu, Bing

AU - Xu, Rui Ming

PY - 2014/6/5

Y1 - 2014/6/5

N2 - Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

AB - Methylated cytosine of CpG dinucleotides in vertebrates may be oxidized by Tet proteins, a process that can lead to DNA demethylation. The predominant oxidation product, 5-hydroxymethylcytosine (5hmC), has been implicated in embryogenesis, cell differentiation, and human diseases. Recently, the SRA domain of UHRF2 (UHRF2-SRA) has been reported to specifically recognize 5hmC, but how UHRF2 recognizes this modification is unclear. Here we report the structure of UHRF2-SRA in complex with a 5hmC-containing DNA. The structure reveals that the conformation of a phenylalanine allows the formation of an optimal 5hmC binding pocket, and a hydrogen bond between the hydroxyl group of 5hmC and UHRF2-SRA is critical for their preferential binding. Further structural and biochemical analyses unveiled the role of SRA domains as a versatile reader of modified DNA, and the knowledge should facilitate further understanding of the biological function of UHRF2 and the comprehension of DNA hydroxymethylation in general.

UR - https://www.scopus.com/pages/publications/84901950311

U2 - 10.1016/j.molcel.2014.04.003

DO - 10.1016/j.molcel.2014.04.003

M3 - 文章

C2 - 24813944

AN - SCOPUS:84901950311

SN - 1097-2765

VL - 54

SP - 879

EP - 886

JO - Molecular Cell

JF - Molecular Cell

IS - 5

ER -

Structural Basis for Hydroxymethylcytosine Recognition by the SRA Domain of UHRF2

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this