2. Academic Validation
  3. ZNF445 is a primary regulator of genomic imprinting

ZNF445 is a primary regulator of genomic imprinting

  • Genes Dev. 2019 Jan 1;33(1-2):49-54. doi: 10.1101/gad.320069.118.
Nozomi Takahashi # 1,  Andrea Coluccio # 2,  Christian W Thorball 2,  Evarist Planet 2,  Hui Shi 1,  Sandra Offner 2,  Priscilla Turelli 2,  Michael Imbeault 1,  Anne C Ferguson-Smith # 1,  Didier Trono # 2
Affiliations

Affiliations

  • 1 Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom.
  • 2 School of Life Sciences, Ecole Polytechnique Federale de Lausanne (EPFL), Lausanne 1015, Switzerland.
  • # Contributed equally.
PMID: 30602440 DOI: 10.1101/gad.320069.118
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.

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