Transcriptional control of TFF3 (intestinal trefoil factor) via promoter binding sites for the nuclear factor kappaB and C/EBPbeta.

摘要

The acute phase response is strictly connected with modulation of gene expression. Transcriptional control of many genes is mediated by binding of diverse transcription factors to cis-acting DNA motifs in the respective promoter sequence. We now describe such regulatory elements for the TFF3 gene coding for a peptide involved in response to gut irritation. TNF-alpha stimulation, which induces NF-kappaB activation, evoked up to 10-fold reduction of TFF3 expression in the colon tumour cell line HT-29. Several consensus binding sites for members of the NF-kappaB transcription factor subunits are located in the 5'-flanking region of TFF3. Mutating these sites was aimed at discovering which one is responsible for NF-kappaB binding and thus regulation of TFF3 expression.