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DOI10.1073/pnas.2005377118
ZFP57 dictates allelic expression switch of target imprinted genes
Jiang W.; Shi J.; Zhao J.; Wang Q.; Cong D.; Chen F.; Zhang Y.; Liu Y.; Zhao J.; Chen Q.; Gu L.; Zhou W.; Wang C.; Fang Z.; Geng S.; Xie W.; Chen L.-N.; Yang Y.; Bai Y.; Lin H.; Li X.
发表日期2021
ISSN00278424
卷号118期号:5
英文摘要ZFP57 is a master regulator of genomic imprinting. It has both maternal and zygotic functions that are partially redundant in maintaining DNA methylation at some imprinting control regions (ICRs). In this study, we found that DNA methylation was lost at most known ICRs in Zfp57 mutant embryos. Furthermore, loss of ZFP57 caused loss of parent-of-origin–dependent monoallelic expression of the target imprinted genes. The allelic expression switch occurred in the ZFP57 target imprinted genes upon loss of differential DNA methylation at the ICRs in Zfp57 mutant embryos. Specifically, upon loss of ZFP57, the alleles of the imprinted genes located on the same chromosome with the originally methylated ICR switched their expression to mimic their counterparts on the other chromosome with unmethylated ICR. Consistent with our previous study, ZFP57 could regulate the NOTCH signaling pathway in mouse embryos by impacting allelic expression of a few regulators in the NOTCH pathway. In addition, the imprinted Dlk1 gene that has been implicated in the NOTCH pathway was significantly down-regulated in Zfp57 mutant embryos. Our allelic expression switch models apply to the examined target imprinted genes controlled by either maternally or paternally methylated ICRs. Our results support the view that ZFP57 controls imprinted expression of its target imprinted genes primarily through maintaining differential DNA methylation at the ICRs. © 2021 National Academy of Sciences. All rights reserved.
英文关键词Allelic expression; Bisulfite sequencing; COBRA; Genomic imprinting; RNA-seq
语种英语
来源期刊Proceedings of the National Academy of Sciences of the United States of America
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/180839
作者单位School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China; Chinese Academy of Sciences Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, CAS, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Center for Stem Cell Biology and Regenerative Medicine, Ministry of Education Key Laboratory of Bioinformatics, Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, 100084, China; Department of Orthopedic Surgery, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China
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Jiang W.,Shi J.,Zhao J.,et al. ZFP57 dictates allelic expression switch of target imprinted genes[J],2021,118(5).
APA Jiang W..,Shi J..,Zhao J..,Wang Q..,Cong D..,...&Li X..(2021).ZFP57 dictates allelic expression switch of target imprinted genes.Proceedings of the National Academy of Sciences of the United States of America,118(5).
MLA Jiang W.,et al."ZFP57 dictates allelic expression switch of target imprinted genes".Proceedings of the National Academy of Sciences of the United States of America 118.5(2021).
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