Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.

ABSTRACT:

Background

Inducible gene expression circuits enable precise control over target gene activation and are widely used in direct reprogramming. However, their usability is often compromised by DNA methylation-induced silencing, especially in iPSCs. This deactivates genetic circuits in engineered iPSCs preventing them from being used for long-term scalable expansion of desired cell types. A2-ubiquitous chromatin opening elements (A2UCOE) have been recognized for their anti-silencing properties, but they have not been used in human iPSCs with inducible systems for direct reprogramming. This study investigates the role of A2UCOE in inducible systems and identifies strategies to eliminate associated gene leakage enabling long-term use of engineered human iPSCs.

Results

We develope

SUBMITTER: Yanagi T 

PROVIDER: S-EPMC11983960 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature