» Articles » PMID: 27257070

ZFP57 Maintains the Parent-of-origin-specific Expression of the Imprinted Genes and Differentially Affects Non-imprinted Targets in Mouse Embryonic Stem Cells

Abstract

ZFP57 is necessary for maintaining repressive epigenetic modifications at Imprinting control regions (ICRs). In mouse embryonic stem cells (ESCs), ZFP57 binds ICRs (ICRBS) and many other loci (non-ICRBS). To address the role of ZFP57 on all its target sites, we performed high-throughput and multi-locus analyses of inbred and hybrid mouse ESC lines carrying different gene knockouts. By using an allele-specific RNA-seq approach, we demonstrate that ZFP57 loss results in derepression of the imprinted allele of multiple genes in the imprinted clusters. We also find marked epigenetic differences between ICRBS and non-ICRBS suggesting that different cis-acting regulatory functions are repressed by ZFP57 at these two classes of target loci. Overall, these data demonstrate that ZFP57 is pivotal to maintain the allele-specific epigenetic modifications of ICRs that in turn are necessary for maintaining the imprinted expression over long distances. At non-ICRBS, ZFP57 inactivation results in acquisition of epigenetic features that are characteristic of poised enhancers, suggesting that another function of ZFP57 in early embryogenesis is to repress cis-acting regulatory elements whose activity is not yet required.

Citing Articles

The role of imprinting genes' loss of imprints in cancers and their clinical implications.

Xie G, Si Q, Zhang G, Fan Y, Li Q, Leng P Front Oncol. 2024; 14:1365474.

PMID: 38812777 PMC: 11133587. DOI: 10.3389/fonc.2024.1365474.


Investigating the potential of single-cell DNA methylation data to detect allele-specific methylation and imprinting.

Johnson N, Cutler D, Conneely K Am J Hum Genet. 2024; 111(4):654-667.

PMID: 38471507 PMC: 11023823. DOI: 10.1016/j.ajhg.2024.02.009.


Auto-suppression of Tet dioxygenases protects the mouse oocyte genome from oxidative demethylation.

Zhang X, Han B, Shao Z, Yan R, Gao J, Liu T Nat Struct Mol Biol. 2024; 31(1):42-53.

PMID: 38177668 DOI: 10.1038/s41594-023-01125-1.


Mutations in human DNA methyltransferase DNMT1 induce specific genome-wide epigenomic and transcriptomic changes in neurodevelopment.

Davis K, Qu P, Ma S, Lin L, Plastini M, Dahl N Hum Mol Genet. 2023; 32(21):3105-3120.

PMID: 37584462 PMC: 10586194. DOI: 10.1093/hmg/ddad123.


Human IGF2 Gene Epigenetic and Transcriptional Regulation: At the Core of Developmental Growth and Tumorigenic Behavior.

Scalia P, Williams S, Fujita-Yamaguchi Y Biomedicines. 2023; 11(6).

PMID: 37371750 PMC: 10296432. DOI: 10.3390/biomedicines11061655.


References
1.
Liu Y, Toh H, Sasaki H, Zhang X, Cheng X . An atomic model of Zfp57 recognition of CpG methylation within a specific DNA sequence. Genes Dev. 2012; 26(21):2374-9. PMC: 3489995. DOI: 10.1101/gad.202200.112. View

2.
Takikawa S, Wang X, Ray C, Vakulenko M, Bell F, Li X . Human and mouse ZFP57 proteins are functionally interchangeable in maintaining genomic imprinting at multiple imprinted regions in mouse ES cells. Epigenetics. 2013; 8(12):1268-79. PMC: 3933488. DOI: 10.4161/epi.26544. View

3.
Habibi E, Brinkman A, Arand J, Kroeze L, Kerstens H, Matarese F . Whole-genome bisulfite sequencing of two distinct interconvertible DNA methylomes of mouse embryonic stem cells. Cell Stem Cell. 2013; 13(3):360-9. DOI: 10.1016/j.stem.2013.06.002. View

4.
Smallwood S, Tomizawa S, Krueger F, Ruf N, Carli N, Segonds-Pichon A . Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet. 2011; 43(8):811-4. PMC: 3146050. DOI: 10.1038/ng.864. View

5.
Proudhon C, Duffie R, Ajjan S, Cowley M, Iranzo J, Carbajosa G . Protection against de novo methylation is instrumental in maintaining parent-of-origin methylation inherited from the gametes. Mol Cell. 2012; 47(6):909-20. PMC: 3778900. DOI: 10.1016/j.molcel.2012.07.010. View