Metabolite changes signal genetic regulatory mechanisms for robust cell behavior.
Exploiting mechanisms of utilizing the sugar d-galactose in Escherichia coli as a model system, we explored the consequences of accumulation of critical intermediates of the d-galactose metabolic pathways by monitoring cell growth, metabolites, and transcript profiles. These studies revealed both metabolic network changes far from the d-galactose pathway and changes in the global gene regulatory network. The concentration change of a critical intermediate disturbs the equilibrium state, generating a ripple effect through several metabolic pathways that ends up signaling up- or downregulation of specific sets of genes in a programmed manner to cope with the imbalance. Such long-range effects on metabolites and genetic regulatory mechanisms not only may be a common feature in bacteria but very likely operate during cellular development and differentiation in higher organisms as well as in disease cells, like cancer cells.


OBJECTIVE
Metabolite accumulation can create adverse intracellular conditions that are relieved by compensatory immediate changes of metabolite pools and later changes of transcript levels. It has been known that gene expression is normally regulated by added catabolic substrates (induction) or anabolic end products (repression). It is becoming apparent now that change in the concentration of metabolic intermediates also plays a critical role in genetic regulatory networks for metabolic homeostasis. Our study provides new insight into how metabolite pool changes transduce signals to global gene regulatory networks.
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic Korea.
Sang Jun
SJ
Lee
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland, USA.
Andrei
A
Trostel
Laboratory of Molecular Biology, National Cancer Institute, Bethesda, Maryland, USA. sadhya@helix.nih.gov
Sankar
S
Adhya
D000222:Adaptation, Physiological; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D005690:Galactose / Q000378:metabolism*; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks
D005690:Galactose