CRISPRa-mediated disentanglement of the Dux-MERVL axis in the 2C-like state, totipotency, and cell death.

ABSTRACT: Transposable elements (TEs) are powerful cis-regulatory drivers of gene expression, particularly during early development when many TEs become de-repressed. MERVL elements are transiently up-regulated in mouse totipotent two-cell (2C) embryos during major zygotic genome activation (ZGA) and 2C-like cells in vitro. One of the most powerful activators of MERVL is the pioneer transcription factor, Dux. However, apparent differences lie in the requirement for Dux versus MERVL activation in embryos. Moreover, sustained Dux activation causes cell toxicity, which may or may not be linked to MERVL. Using a CRISPR activation system, we unpick the relative role of Dux and MERVL in ZGA, totipotent-like characteristics, and cell toxicity. We find that MERVL activation drives a portion of the Dux-depen

SUBMITTER: Chammas P 

PROVIDER: S-EPMC12716392 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature