A suboptimal OCT4-SOX2 binding site facilitates the naive-state specific function of a Klf4 enhancer.

ABSTRACT: Enhancers have critical functions in the precise, spatiotemporal control of transcription during development. It is thought that enhancer grammar, or the characteristics and arrangements of transcription factor binding sites, underlie the specific functions of developmental enhancers. In this study, we sought to identify grammatical constraints that direct enhancer activity in the naïve state of pluripotency, focusing on the enhancers for the naïve-state specific gene, Klf4. Using a combination of biochemical tests, reporter assays, and endogenous mutations in mouse embryonic stem cells, we have studied the binding sites for the transcription factors OCT4 and SOX2. We have found that the three Klf4 enhancers contain suboptimal OCT4-SOX2 composite binding sites. Substitution with a high-aff

SUBMITTER: Waite JB 

PROVIDER: S-EPMC11441684 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature