H-049. Signal Integration in the Galactose Network of Escherichia coli

S. Semsey1, S. Krishna2, K. Sneppen2, S. Adhya3;
1ELTE, Budapest, HUNGARY, 2CMOL/NBI, Copenhagen, DENMARK, 3NCI, Bethesda, MD.

The gal regulon of E. coli contains genes involved in galactose transport and metabolism. Transcription of the gal regulon genes is regulated in different ways by two iso-regulatory proteins, GalR and GalS, which recognize the same binding sites in the absence of D-galactose. DNA binding by both GalR and GalS is inhibited in the presence of D-galactose. Many of the gal regulon genes are activated in the presence of the cAMP-CRP complex. We studied transcriptional regulation of the gal regulon promoters simultaneously in a purified system and attempted to integrate the two small molecule signals, cAMP and D-galactose that modulate the isoregulators and CRP respectively, at each promoter, using Boolean logic. Seven of the sixteen possible logic gates occur naturally in the Galactose network. Results show that similarly organized promoters can have different input functions. We also found that in some cases the activity of the promoter and the cognate gene can be described by different logic gates. We combined the transcriptional network of the galactose regulon, obtained from our experiments, with literature data to construct the map of the galactose network. This integrated network contains both the metabolic and regulatory interactions. Analysis of the network suggests that GalR is the primary regulator for the steady-state levels of promoter activities. The role of GalS therefore should lie either in more graded features of the response or in transient dynamics. To elucidate the role of GalS, we aim to construct a quantitative model of the galactose network.