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

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

iScience (2022-08-24)
Alla V Tsytsykova, Graham Wiley, Chuang Li, Richard C Pelikan, Lori Garman, Francis A Acquah, Blaine H M Mooers, Erdyni N Tsitsikov, Ian F Dunn
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 (KLF4K409Q) 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 KLF4K409Q-specific targets, the normally silent fibroblast growth factor 3 (FGF3) is activated. We demonstrated a neomorphic function of KLF4K409Q in stimulating FGF3 transcription through binding to its promoter and in using short tandem repeats (STRs) located within the locus as enhancers.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
KLF4-TAT human, recombinant, expressed in HEK 293 cells, ≥90% (SDS-PAGE), ≥90% (HPLC), suitable for cell culture
Sigma-Aldrich
Anti-SP3, C-Terminal antibody produced in rabbit, affinity isolated antibody
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2 antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Millipore
Anti-FLAG® M2 Magnetic Beads, affinity isolated antibody
Sigma-Aldrich
Monoclonal ANTI-FLAG® M2-Peroxidase (HRP) antibody produced in mouse, clone M2, purified immunoglobulin, buffered aqueous glycerol solution
Sigma-Aldrich
Anti-KLF4 antibody produced in rabbit, saturated ammonium sulfate (SAS) precipitated, buffered aqueous solution
Sigma-Aldrich
Anti-Sp1 Antibody, Upstate®, from rabbit
Roche
β-Gal Reporter Gene Assay, chemiluminescent, sufficient for 500 assays (microplate), sufficient for 250 assays (tubes)
Sigma-Aldrich
Anti-KLF4 antibody produced in rabbit, affinity isolated antibody