ZNF445 is a primary regulator of genomic imprinting.
Thorball, Christian W
Ferguson-Smith, Anne C
Cold Spring Harbor Laboratory
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Takahashi, N., Coluccio, A., Thorball, C. W., Planet, E., Shi, H., Offner, S., Turelli, P., et al. (2019). ZNF445 is a primary regulator of genomic imprinting.. Genes Dev, 33 (1-2), 49-54. https://doi.org/10.1101/gad.320069.118
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.
Cells, Cultured, Animals, Mice, Inbred C57BL, Humans, Mice, Transcription Factors, Repressor Proteins, DNA Methylation, Genomic Imprinting, Conserved Sequence, Kruppel-Like Transcription Factors, Embryonic Stem Cells, HEK293 Cells
Medical Research Council (MR/J001597/1)
Wellcome Trust (095606/Z/11/Z)
European Commission (290123)
Medical Research Council (MR/R009791/1)
External DOI: https://doi.org/10.1101/gad.320069.118
This record's URL: https://www.repository.cam.ac.uk/handle/1810/288175
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/