ZFP57 dictates allelic expression switch of target imprinted genes
- 26 January 2021
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 118 (5)
- https://doi.org/10.1073/pnas.2005377118
Abstract
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.Funding Information
- Ministry of Science and Technology of the People's Republic of China (# 2018YFC1005004)
- Science and Technology Commission of Shanghai Municipality (18PJ1407700)
- National Natural Science Foundation of China (31670756)
This publication has 57 references indexed in Scilit:
- Epigenetic regulation of genomic imprinting from germ line to preimplantationMolecular Reproduction and Development, 2013
- Imprinted silencing is extended over broad chromosomal domains in mouse extra-embryonic lineagesCurrent Opinion in Cell Biology, 2013
- Genomic imprinting and its relevance to congenital disease, infertility, molar pregnancy and induced pluripotent stem cellJournal of Human Genetics, 2012
- In Embryonic Stem Cells, ZFP57/KAP1 Recognize a Methylated Hexanucleotide to Affect Chromatin and DNA Methylation of Imprinting Control RegionsMolecular Cell, 2011
- Activation of the Imprinted Dlk1-Dio3 Region Correlates with Pluripotency Levels of Mouse Stem CellsOnline Journal of Public Health Informatics, 2010
- A Maternal-Zygotic Effect Gene, Zfp57, Maintains Both Maternal and Paternal ImprintsDevelopmental Cell, 2008
- Gender influences monoallelic expression of ATP10A in human brainHuman Genetics, 2008
- Capturing PluripotencyCell, 2008
- Imprinting on distal chromosome 7 in the placenta involves repressive histone methylation independent of DNA methylationNature Genetics, 2004
- Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexesNature Genetics, 2004