Mutated KLF4(K409Q) in meningioma binds STRs and activates FGF3 gene expression.

ABSTRACT: Krüppel-like factor 4 (KLF4) is a transcription factor that has been proven necessary for both induction and maintenance of pluripotency and self-renewal. Whole-genome sequencing defined a unique mutation in KLF4 (KLF4^K409Q) in human meningiomas. However, the molecular mechanism of this tumor-specific KLF4 mutation is unknown. Using genome-wide high-throughput and focused quantitative transcriptional approaches in human cell lines, primary meningeal cells, and meningioma tumor tissue, we found that a change in the evolutionarily conserved DNA-binding domain of KLF4 alters its DNA recognition preference, resulting in a shift in downstream transcriptional activity. In the KLF4^K409Q-specific targets, the normally silent fibroblast growth factor 3 (FGF3) is activat

SUBMITTER: Tsytsykova AV 

PROVIDER: S-EPMC9391581 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature