ssRNA and dbDNA SELEX against FOXL2 and the oncogenic variant C134W (mutFOXl2). ssRNA and dbDNA SELEX against the wildtype FOXL2 and the oncogenic variant C134W (mutFOXl2)

The family of forkhead (FOX) transcription factors is composed of dozens of paralogs in mammals. The forkhead domain (FHD) involves a segment of about 100 amino acids that binds an A-rich DNA sequence. Using dbDNA and ssRNA SELEX, we show that recombinant FOXL2 proteins, either wild-type or carrying the oncogenic variant C134W, recognize similar DNA-binding sites. This suggests that the oncogenic mutation does not alter the intrinsic sequence-specificity of FOXL2. Most importantly, we show that FOXL2 binds G2-rich RNA sequences that are predicted to fold into G-quadruplexes (rG4) whereas it fails to bind similar sequences in DNA chemistry.