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 journal › Journal article › Research › peer-review
Standard
ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells. / Riso, Vincenzo; Cammisa, Marco; Kukreja, Harpreet; Anvar, Zahra; Verde, Gaetano; Sparago, Angela; Acurzio, Basilia; Lad, Shraddha; Lonardo, Enza; Sankar, Aditya; Helin, Kristian; Feil, Robert; Fico, Annalisa; Angelini, Claudia; Grimaldi, Giovanna; Riccio, Andrea.
In: Nucleic Acids Research, Vol. 44, No. 17, 01.06.2016, p. 8165-8178.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - ZFP57 maintains the parent-of-origin-specific expression of the imprinted genes and differentially affects non-imprinted targets in mouse embryonic stem cells
AU - Riso, Vincenzo
AU - Cammisa, Marco
AU - Kukreja, Harpreet
AU - Anvar, Zahra
AU - Verde, Gaetano
AU - Sparago, Angela
AU - Acurzio, Basilia
AU - Lad, Shraddha
AU - Lonardo, Enza
AU - Sankar, Aditya
AU - Helin, Kristian
AU - Feil, Robert
AU - Fico, Annalisa
AU - Angelini, Claudia
AU - Grimaldi, Giovanna
AU - Riccio, Andrea
N1 - © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - 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.
AB - 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.
U2 - 10.1093/nar/gkw505
DO - 10.1093/nar/gkw505
M3 - Journal article
C2 - 27257070
VL - 44
SP - 8165
EP - 8178
JO - Nucleic Acids Research
JF - Nucleic Acids Research
SN - 0305-1048
IS - 17
ER -
ID: 165702653