Inhibition of human proinsulin promoter activity by Krueppel-like transcription factor 11 (KLF11) is mediated through functional interactions with PDX-1 and a proximal CACCC box

Background: Krueppel-like transcription factor 11 (KLF11, TIEG2) is a member of the Sp1/KLF transcription factor family which plays an important role in mammalian gene regulation via binding to GC-rich promoter elements comprising CGCCC (GC) or CACCC box core sequences. Previously we demonstrated that human KLF11 (hKLF11) inhibits human proinsulin promoter activity in rodent beta-cell lines (INS-1, beta-TC3). At insulin gene upstream sequences hKLF11 binds to a GC box but not to a proximal CACCC box. Surprisingly, deletion and mutation of the GC box did not alter hKLF11-mediated inhibition of proinsulin promoter…