ZNF445 is a primary regulator of genomic imprinting
- Nozomi Takahashi1,3,
- Andrea Coluccio2,3,
- Christian W. Thorball2,
- Evarist Planet2,
- Hui Shi1,
- Sandra Offner2,
- Priscilla Turelli2,
- Michael Imbeault1,
- Anne C. Ferguson-Smith1,4 and
- Didier Trono2,4
- 1Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom;
- 2School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne 1015, Switzerland
- Corresponding authors: afsmith{at}gen.cam.ac.uk, didier.trono{at}epfl.ch
Abstract
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.
Keywords
- KRAB zinc finger proteins
- ZFP445
- ZFP57
- genomic imprint maintenance
- resistance to epigenetic reprogramming
Footnotes
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Supplemental material is available for this article.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.320069.118.
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Freely available online through the Genes & Development Open Access option.
- Received August 22, 2018.
- Accepted November 7, 2018.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
