Zfp57 inactivation illustrates the role of ICR methylation in imprinted gene expression during neural differentiation of mouse ESCs

Author:

Acurzio Basilia,Verma Ankit,Polito Alessia,Giaccari Carlo,Cecere Francesco,Fioriniello Salvatore,Della Ragione Floriana,Fico Annalisa,Cerrato Flavia,Angelini Claudia,Feil Robert,Riccio Andrea

Abstract

AbstractZFP57 is required to maintain the germline-marked differential methylation at imprinting control regions (ICRs) in mouse embryonic stem cells (ESCs). Although DNA methylation has a key role in genomic imprinting, several imprinted genes are controlled by different mechanisms, and a comprehensive study of the relationship between DMR methylation and imprinted gene expression is lacking. To address the latter issue, we differentiated wild-type and Zfp57-/- hybrid mouse ESCs into neural precursor cells (NPCs) and evaluated allelic expression of imprinted genes. In mutant NPCs, we observed a reduction of allelic bias of all the 32 genes that were imprinted in wild-type cells, demonstrating that ZFP57-dependent methylation is required for maintaining or acquiring imprinted gene expression during differentiation. Analysis of expression levels showed that imprinted genes expressed from the non-methylated chromosome were generally up-regulated, and those expressed from the methylated chromosome were down-regulated in mutant cells. However, expression levels of several imprinted genes acquiring biallelic expression were not affected, suggesting the existence of compensatory mechanisms that control their RNA level. Since neural differentiation was partially impaired in Zfp57-mutant cells, this study also indicates that imprinted genes and/or non-imprinted ZFP57-target genes are required for proper neurogenesis in cultured ESCs.

Funder

Università degli Studi della Campania "Luigi Vanvitelli”

Regione Campania

Fondation pour la Recherche Médicale

Associazione Italiana per la Ricerca sul Cancro

Fondazione Telethon

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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