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J Biol Chem. 2016 Jun 24;291(26):13679-88. doi: 10.1074/jbc.M116.717314. Epub 2016 Apr 27.

Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader.

Author information

1
From the Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, China, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China and.
2
Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, California 91010.
3
From the Key Laboratory of Reproductive Genetics, Ministry of Education and Women's Reproductive Health Laboratory of Zhejiang Province, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310006, China, Institute of Translational Medicine, Zhejiang University, Hangzhou, Zhejiang, 310029, China and lulinyu@zju.edu.cn.
4
Department of Cancer Genetics and Epigenetics, Beckman Research Institute, City of Hope, Duarte, California 91010 xyu@coh.org.

Abstract

5-Hydroxymethylcytosine (5hmC) is an epigenetic modification that is generated by ten-eleven translocation (TET) protein-mediated oxidation of 5-methylcytosine (5mC). 5hmC is associated with transcription regulation and is decreased in many cancers including melanoma. Accumulating evidence has suggested that 5hmC is functionally distinct from 5mC. Ubiquitin-like with PHD and ring finger domains 2 (UHRF2) is the first known specific 5hmC reader that has higher affinity to 5hmC than 5mC, suggesting that UHRF2 might mediate 5hmC's function. Structural analysis has revealed the molecular mechanism of UHRF2-5hmC binding in vitro, but it is not clear how UHRF2 recognizes 5hmC in vivo In this study, we have identified zinc figure protein 618 (ZNF618) as a novel binding partner of UHRF2. ZNF618 specifically interacts with UHRF2 but not its paralog UHRF1. Importantly, ZNF618 co-localizes with UHRF2 at genomic loci that are enriched for 5hmC. The ZNF618 chromatin localization is independent of its interaction with UHRF2 and is through its first two zinc fingers. Instead, ZNF618 regulates UHRF2 chromatin localization. Collectively, our study suggests that ZNF618 is a key protein that regulates UHRF2 function as a specific 5hmC reader in vivo.

KEYWORDS:

5-hydroxymethylcytosine (5-hmC); DNA demethylation; chromatin; molecular biology; molecular cell biology

PMID:
27129234
PMCID:
PMC4919451
DOI:
10.1074/jbc.M116.717314
[Indexed for MEDLINE]
Free PMC Article

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