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Hum Mol Genet. 2018 Feb 1;27(3):505-515. doi: 10.1093/hmg/ddx420.

Zinc finger protein 274 regulates imprinted expression of transcripts in Prader-Willi syndrome neurons.

Author information

1
Department of Genetics and Genome Sciences, School of Medicine.
2
Institute for Systems Genomics, University of Connecticut, Farmington, CT 06030-6403, USA.

Abstract

Prader-Willi syndrome (PWS) is characterized by neonatal hypotonia, developmental delay and hyperphagia/obesity and is caused by the absence of paternal contribution to chromosome 15q11-q13. Using induced pluripotent stem cell (iPSC) models of PWS, we previously discovered an epigenetic complex that is comprised of the zinc-finger protein ZNF274 and the SET domain bifurcated 1 (SETDB1) histone H3 lysine 9 (H3K9) methyltransferase and that silences the maternal alleles at the PWS locus. Here, we have knocked out ZNF274 and rescued the expression of silent maternal alleles in neurons derived from PWS iPSC lines, without affecting DNA methylation at the PWS-Imprinting Center (PWS-IC). This suggests that the ZNF274 complex is a separate imprinting mark that represses maternal PWS gene expression in neurons and is a potential target for future therapeutic applications to rescue the PWS phenotype.

PMID:
29228278
DOI:
10.1093/hmg/ddx420
[Indexed for MEDLINE]

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