TY  - JOUR
A1  - Yoon, Sung Ho
A1  - Turkarslan, Serdar
A1  - Reiss, David J.
A1  - Pan, Min
A1  - Burn, June A.
A1  - Costa, Kyle C.
A1  - Lie, Thomas J.
A1  - Slagel, Joseph
A1  - Moritz, Robert L.
A1  - Hackett, Murray
A1  - Leigh, John A.
A1  - Baliga, Nitin S.
T1  - A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen
Y1  - 2013/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 1839 
EP  - 1851 
DO  - 10.1101/gr.153916.112 
VL  - 23 
IS  - 11 
UR  - http://genome.cshlp.org/content/23/11/1839.abstract 
N2  - 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, Methanococcus maripaludis. We generated a comprehensive list of genes (protein-coding and noncoding) for M. maripaludis 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. 
ER  -