Zfp57 Exerts Maternal and Sexually Dimorphic Effects on Genomic Imprinting.

Zhen Xu,Yun Bai,Junzheng Zhao,Qian Chen,Feizhen Wu,Yuhan Liu,Wei Xie,Xiajun Li,Yu Zhang,Shuhui Geng,Jiajia Shi,Chenglin Song,Yang Yang

doi:10.3389/fcell.2022.784128

Abstract

Zfp57 has both maternal and zygotic functions in mouse. It maintains genomic imprinting at most known imprinted regions and controls allelic expression of the target imprinted genes in mouse embryos. The DNA methylation imprint at many imprinting control regions (ICRs) is lost when both maternal and zygotic Zfp57 are absent in Zfp57 maternal–zygotic mutant mouse embryos. Interestingly, we found that DNA methylation at a few ICRs was partially lost without maternal Zfp57 in Zfp57 heterozygous mouse embryos derived from Zfp57 homozygous female mice. This suggests that maternal Zfp57 is essential for the maintenance of DNA methylation at a small subset of imprinted regions in mouse embryos. This maternal effect of Zfp57 was applied to allelic expression switch as well as expression levels of the corresponding imprinted genes. It is rather surprising that DNA methylation imprint was affected differently at Rasgrf1 and AK008011 imprinted regions in the female or male Zfp57 maternal–zygotic mutant embryos, with more significant loss of DNA methylation observed in the male mutant embryos. Loss of ZFP57 resulted in gender-specific differences in allelic expression switch and expression level changes of some imprinted genes in female or male mutant embryos. These results indicate maternal and sexually dimorphic effects of ZFP57 on genomic imprinting in mouse.

Highlights

Genomic imprinting is a kind of parental effect on the progeny that is established in the female or male germline (Bartolomei and Ferguson-Smith, 2011; Li, 2013; Tucci et al, 2019)
Whole-genome bisulfite sequencing (WGBS) was performed to examine DNA methylation in the 129/DBA hybrid Zfp57+/− (M+Z+), Zfp57−/+ (M−Z+), and Zfp57−/− (M−Z−) embryos derived from timed mating with Zfp57+/− or Zfp57−/− 129 female mice being crossed with Zfp57+/− (DBA*) male mice mainly on the DBA/2J genetic background as reported in the previous study (Jiang et al, 2021)
There was no significant difference in DNA methylation at all 24 known imprinting control regions (ICRs) comparing female M+Z+ embryos with the male M+Z+ embryos, except that DNA methylation was slightly significantly increased at the Nap1I5 ICR but decreased at the Grb10 ICR in the male M+Z+ embryos compared with the female M+Z+ embryos

Summary

Introduction

Genomic imprinting is a kind of parental effect on the progeny that is established in the female or male germline (Bartolomei and Ferguson-Smith, 2011; Li, 2013; Tucci et al, 2019). It is essential for mammalian embryonic growth and development. Most of approximately 150 known imprinted genes are clustered in over 20 known imprinted regions with each harboring a few imprinted genes (Monk et al, 2019) They are co-regulated by a cis-acting imprinting control region (ICR) containing germline-derived differential DNA methylation (Barlow and Bartolomei, 2014; Zeng and Chen, 2019).

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Results

Conclusion