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ZFP57 dictates allelic expression switch of target imprinted genes

Weijun Jiang, Jiajia Shi, Jingjie Zhao, Qiu Wang, Dan Cong, Fenghua Chen, Yu Zhang, Yuhan Liu, Junzheng Zhao, Qian Chen, Linhao Gu, Wenjia Zhou, Chenhang Wang, Zhaoyuan Fang, Shuhui Geng, Wei Xie, Luonan Chen, Yang Yang, Yun Bai, Haodong Lin, Xiajun Li

2021Proceedings of the National Academy of Sciences26 citationsDOIOpen Access PDF

Abstract

Significance This study provides further proof for ZFP57 as a master regulator of genomic imprinting since it maintains DNA methylation at most known imprinted regions and regulates allelic expression of the corresponding imprinted genes. We propose two alternate allelic switch models for ZFP57-dependent regulation of parent-of-origin–dependent expression of the imprinted genes based on allelic and quantitative expression analyses of the imprinted genes. Our results also shed light on the mechanistic link between DNA methylation imprint and monoallelic expression of the imprinted genes. The results indicate that ZFP57 regulates allelic expression of clustered imprinted genes through maintenance of DNA methylation at the imprinting control regions.

Topics & Concepts

Genomic imprintingImprinting (psychology)BiologyDNA methylationAlleleGeneGeneticsMethylationGene expressionRegulation of gene expressionGenetic Syndromes and ImprintingEpigenetics and DNA MethylationPrenatal Screening and Diagnostics