Reversing transgene silencing via targeted chromatin editing.

ABSTRACT: Mammalian cell engineering offers the opportunity to uncover biological principles and develop next-generation biotechnologies. However, epigenetic silencing of transgenes hinders the control of gene expression in mammalian cells. Here, we use chromatin editing of an integrated reporter in CHO-K1 and human induced pluripotent stem cells to study the molecular interactions driving silencing and its reversal. After transient induction of either DNA methylation or H3K9me3, stable silencing was exclusively observed with both marks. Due to the positive feedback between DNA methylation and H3K9me3 and the relative low stability of H3K9me3, our model predicts that removing DNA methylation is sufficient for transgene reactivation. Accordingly, targeted DNA demethylation reactivated the reporter ir

SUBMITTER: Palacios S 

PROVIDER: S-EPMC12636370 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature