ArticleStem cell reports2026
The imprinted Peg3 gene is a potent regulator of the DNA methylome in trophoblast cells.
Article in Stem cell reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Paternally expressed gene 3 (Peg3) is an imprinted gene whose knockout (KO) causes placental and fetal growth deficits as well as maternal behavioral defects, but its molecular role remains poorly understood. Here, we report that Peg3-null trophoblast stem cells (TSCs) exhibit increased rates of mitotic errors and double-strand DNA breaks as a likely consequence of a global reduction in H3K9me3 and DNA methylation levels. Transcriptional profiling highlights a deficiency of KO cells to adequately silence genes, resulting in elevated expression levels of differentiation stage-inappropriate genes. Peg3 KO TSCs also exhibit a loss of DNA methylation and H3K9me3 at a subset of developmentally regulated CpG islands that likely rewire CTCF-regulated transcriptional networks. Collectively, our data identify PEG3 as an intrinsic component of the epigenetic repressive machinery, thus solidifying its putative role as a KRAB-ZFP protein that functions to regulate gene expression and genome integrity in the placental trophoblast lineage.
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