2. Academic Validation
  3. Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2

Structural basis for hydroxymethylcytosine recognition by the SRA domain of UHRF2

  • Mol Cell. 2014 Jun 5;54(5):879-86. doi: 10.1016/j.molcel.2014.04.003.
Ting Zhou 1,  Jun Xiong 2,  Mingzhu Wang 3,  Na Yang 3,  Jiemin Wong 4,  Bing Zhu 2,  Rui-Ming Xu 5
Affiliations

Affiliations

  • 1 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 National Institute of Biological Sciences, Beijing 102206, China.
  • 3 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 4 Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai 200241, China.
  • 5 National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: [email protected].
PMID: 24813944 DOI: 10.1016/j.molcel.2014.04.003
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.

Figures