Reporter CRISPR screens decipher cis-regulatory and trans-regulatory principles at the Xist locus.

ABSTRACT: Developmental genes are controlled by an ensemble of cis-acting regulatory elements (REs), which in turn respond to multiple trans-acting transcription factors (TFs). Understanding how a cis-regulatory landscape integrates information from many dynamically expressed TFs has remained a challenge. Here we develop a combined CRISPR screening approach using endogenous RNA and RE reporters as readouts. Applied to the murine Xist locus, which is crucial for X-chromosome inactivation in females, this method allows us to comprehensively identify Xist-controlling TFs and map their TF-RE wiring. We find a group of transiently upregulated TFs, including ZIC3, that regulate proximal REs, driving the binary activation of Xist expression. These basal activators are more highly expressed in cells with tw

SUBMITTER: Schwammle T 

PROVIDER: S-EPMC12700789 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature