ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells

Research output: Contribution to journalJournal articleResearchpeer-review

  • Vincenzo Riso
  • Marco Cammisa
  • Harpreet Kukreja
  • Zahra Anvar
  • Gaetano Verde
  • Angela Sparago
  • Basilia Acurzio
  • Shraddha Lad
  • Enza Lonardo
  • Sankar, Aditya
  • Kristian Helin
  • Robert Feil
  • Annalisa Fico
  • Claudia Angelini
  • Giovanna Grimaldi
  • Andrea Riccio

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.

Original languageEnglish
JournalNucleic Acids Research
Issue number17
Pages (from-to)8165-8178
Number of pages14
Publication statusPublished - 1 Jun 2016

ID: 165702653