How affinity of the ELT-2 GATA factor binding to acting regulatory sites controls intestinal gene transcription.

We define a quantitative relationship between the affinity with which the intestine-specific GATA factor ELT-2 binds to -acting regulatory motifs and the resulting transcription of , a target gene representative of genes involved in intestine differentiation. By establishing an experimental system that allows unknown parameters (e.g. the influence of chromatin) to effectively cancel out, we show that levels of transcripts increase monotonically with increasing binding affinity of ELT-2 to variant promoter TGATAA sites. The shape of the response curve reveals that the product of the unbound ELT-2 concentration [i.e. (ELT-2) or ELT-2 'activity'] and the largest ELT-XXTGATAAXX association constant (K) lies between five and ten. We suggest that this (unitless) product [K×(ELT-2) or the equivalent product for any other transcription factor] provides an important quantitative descriptor of transcription-factor/regulatory-motif interaction in development, evolution and genetic disease. A more complicated model than simple binding affinity is necessary to explain the fact that ELT-2 appears to discriminate against equal-affinity binding sites that contain AGATAA instead of TGATAA.