Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/177824
Title: The role of ZFP57 and additional KRAB-Zinc Finger proteins in the maintenance of human imprinted methylation and multi-locus imprinting disturbances
Author: Monteagudo Sánchez, Ana
Hernandez Mora, Jose Ramon
Simón, Carlos
Burton, Adam
Tenorio, Jair
Lapunzina, Pablo
Clark, Stephen
Esteller, Manel
Kelsey, Gavin
López-Siguero, Juan Pedro
Perez de Nanclares, Guiomar
Torres Padilla, Maria Elena
Keywords: Genòmica
Proteïnes
ADN
Metilació
Genomics
Proteins
DNA
Methylation
Issue Date: 14-Oct-2020
Publisher: Oxford University Press
Abstract: Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation that is resistant to embryonic reprogramming, resulting in parental origin-specific monoallelic gene expression. A subset of individuals affected by imprinting disorders (IDs) displays multi-locus imprinting disturbances (MLID), which may result from aberrant establishment of imprinted differentially methylated regions (DMRs) in gametes or their maintenance in early embryogenesis. Here we investigated the extent of MLID in a family harbouring a ZFP57 truncating variant and characterize the interactions between human ZFP57 and the KAP1 co-repressor complex. By ectopically targeting ZFP57 to reprogrammed loci in mouse embryos using a dCas9 approach, we confirm that ZFP57 recruitment is sufficient to protect oocyte-derived methylation from reprogramming. Expression profiling in human pre-implantation embryos and oocytes reveals that unlike in mice, ZFP57 is only expressed following embryonic-genome activation, implying that other KRAB-zinc finger proteins (KZNFs) recruit KAP1 prior to blastocyst formation. Furthermore, we uncover ZNF202 and ZNF445 as additional KZNFs likely to recruit KAP1 to imprinted loci during reprogramming in the absence of ZFP57. Together, these data confirm the perplexing link between KZFPs and imprint maintenance and highlight the differences between mouse and humans in this respect.
Note: Reproducció del document publicat a: https://doi.org/10.1093/nar/gkaa837
It is part of: Nucleic Acids Research, 2020, vol. 48, num. 20, p. 11394-11407
URI: http://hdl.handle.net/2445/177824
Related resource: https://doi.org/10.1093/nar/gkaa837
ISSN: 0305-1048
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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