title: 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.
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Riso
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cammisa
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kukreja
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Anvar
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Verde
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Sparago
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy.
authors.forename: Basilia
authors.initials: B
authors.lastname: Acurzio
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy.
authors.forename: Shraddha
authors.initials: S
authors.lastname: Lad
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy.
authors.forename: Enza
authors.initials: E
authors.lastname: Lonardo
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark Center for Epigenetics, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Aditya
authors.initials: A
authors.lastname: Sankar
authors.affiliation: Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Copenhagen, Denmark The Danish Stem Cell Center (Danstem), University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Kristian
authors.identifier: 0000-0003-1975-6097
authors.initials: K
authors.lastname: Helin
authors.affiliation: Institute of Molecular Genetics (IGMM), CNRS, 34293 Montpellier, France University of Montpellier, 34090 Montpellier, France.
authors.forename: Robert
authors.initials: R
authors.lastname: Feil
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fico
authors.affiliation: Istituto per le Applicazioni del Calcolo 'Mauro Picone' (IAC), CNR, 80131 Naples, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Angelini
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Ceinge Biotecnologie Avanzate s.c.a.r.l., 80145 Naples, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Grimaldi
authors.affiliation: Institute of Genetics and Biophysics 'A. Buzzati-Traverso', CNR, 80131 Naples, Italy Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, 81100 Caserta, Italy andrea.riccio@unina2.it.
authors.forename: Andrea
authors.identifier: 0000-0001-7990-3576
authors.initials: A
authors.lastname: Riccio
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D044127:Epigenesis, Genetic; D018507:Gene Expression Regulation, Developmental; D056426:Genetic Loci; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D008957:Models, Genetic; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*
chemical_list: D006657:Histones; D009687:Nuclear Proteins; D012097:Repressor Proteins; C501529:Zfp-57 protein, mouse; D008239:Lysine