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Yoon, Sung Ho,Turkarslan, Serdar,Reiss, David J.,Pan, Min,Burn, June A.,Costa, Kyle C.,Lie, Thomas J.,Slagel, Joseph,Moritz, Robert L.,Hackett, Murray,Leigh, John A.,Baliga, Nitin S. Cold Spring Harbor Laboratory Press 2013 Genome research Vol.23 No.11
<P>Methanogens catalyze the critical methane-producing step (called methanogenesis) in the anaerobic decomposition of organic matter. Here, we present the first predictive model of global gene regulation of methanogenesis in a hydrogenotrophic methanogen, <I>Methanococcus maripaludis</I>. We generated a comprehensive list of genes (protein-coding and noncoding) for <I>M. maripaludis</I> through integrated analysis of the transcriptome structure and a newly constructed Peptide Atlas. The environment and gene-regulatory influence network (EGRIN) model of the strain was constructed from a compendium of transcriptome data that was collected over 58 different steady-state and time-course experiments that were performed in chemostats or batch cultures under a spectrum of environmental perturbations that modulated methanogenesis. Analyses of the EGRIN model have revealed novel components of methanogenesis that included at least three additional protein-coding genes of previously unknown function as well as one noncoding RNA. We discovered that at least five regulatory mechanisms act in a combinatorial scheme to intercoordinate key steps of methanogenesis with different processes such as motility, ATP biosynthesis, and carbon assimilation. Through a combination of genetic and environmental perturbation experiments we have validated the EGRIN-predicted role of two novel transcription factors in the regulation of phosphate-dependent repression of formate dehydrogenase—a key enzyme in the methanogenesis pathway. The EGRIN model demonstrates regulatory affiliations within methanogenesis as well as between methanogenesis and other cellular functions.</P>