期刊
GENES & DEVELOPMENT
卷 33, 期 1-2, 页码 49-54出版社
COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.320069.118
关键词
KRAB zinc finger proteins; ZFP445; ZFP57; genomic imprint maintenance; resistance to epigenetic reprogramming
资金
- Herchel Smith Fellowship
- Medical Research Council [MR/J001597/1]
- Wellcome Trust [WT095606]
- People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7 MC-ITN INGENIUM) [290123]
- Swiss National Science Foundation
- European Research Council [ERC 268721, ERC 694658]
- Gebert-Ruf Foundation
- MRC [MR/J001597/1, MR/R009791/1] Funding Source: UKRI
- Medical Research Council [MR/R009791/1, MR/J001597/1] Funding Source: researchfish
Genomic imprinting is an epigenetic process regulated by germline-derived DNA methylation, causing parental origin-specific monoallelic gene expression. Zinc finger protein 57 (ZFP57) is critical for maintenance of this epigenetic memory during post-fertilization reprogramming, yet incomplete penetrance of ZFP57 mutations in humans and mice suggests additional effectors. We reveal that ZNF445/ZFP445, which we trace to the origins of imprinting, binds imprinting control regions (ICRs) in mice and humans. In mice, ZFP445 and ZFP57 act together, maintaining all but one ICR in vivo, whereas earlier embryonic expression of ZNF445 and its intolerance to loss-of-function mutations indicate greater importance in the maintenance of human imprints.
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