Imprint stability and plasticity during development

Abstract

There have been a number of recent insights in the area of genomic imprinting, the phenomenon whereby one of two autosomal alleles is selected for expression based on the parent of origin. This is due in part to a proliferation of new techniques for interrogating the genome that are leading researchers working on organisms other than mouse and human, where imprinting has been most studied, to become interested in looking for potential imprinting effects. Here, we recap what is known about the importance of imprints for growth and body size, as well as the main types of locus control. Interestingly, work from a number of labs has now shown that maintenance of the imprint post implantation appears to be a more crucial step than previously appreciated. We ask whether imprints can be reprogrammed somatically, how many loci there are and how conserved imprinted regions are in other species. Finally, we survey some of the methods available for examining DNA methylation genome-wide and look to the future of this burgeoning field.

ZFP57 dictates allelic expression switch of target imprinted genes

“…Some imprinted genes exhibit tissue-specific imprinted expression (8,(45)(46)(47). Cobl at the Grb10 imprinted region was reported to be only imprinted in mouse yolk sac and we found it was biallelic in mouse embryos (SI Appendix, Fig.…”

“…To date there are about 150 known imprinted genes, with more than half of them conserved between mice and humans (1,3). It is well established that genomic imprinting is required for mammalian sexual reproduction and embryonic development (1,(8)(9)(10). Loss of genomic imprinting causes many human diseases, such as diabetes, cancer, and neurological disorders (11).…”

A randomized controlled trial of folic acid intervention in pregnancy highlights a putative methylation-regulated control element at ZFP57

“…Uncovering a DMR at a region controlling ZFP57 transcription as the top hit in an unbiased screen was particularly striking in the EpiFASSTT randomized controlled trial, where we have already shown, using a candidate gene approach, that methylation levels were perturbed at some imprinted loci. The primary importance of ZFP57, as described in the literature from mechanistic work, is in maintaining imprinting, and it is currently the only protein known to be dedicated solely or largely to this epigenetic process [53]. ZFP57 was discovered as a maternal-zygotic effect gene which was required in mice for establishing methylation at some imprints in the oocyte, and for maintaining all imprints, both maternal and paternal, in the preimplantation embryo [38].…”

Endogenous Retroviruses Walk a Fine Line between Priming and Silencing

“…The murine ERVK family drives non-canonical, histone-dependent imprinting in the extraembryonic lineage [ 61 ]. Imprinted loci are established during epigenetic reprogramming of the germline and persist in the early embryo [ 54 , 62 , 63 ]. In contrast to epialleles, heterochromatin induction at imprinted loci is not stochastic but established at either the paternal or maternal allele, respectively, and is essential for proper development.…”