A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

Sung Ho Yoon, Serdar Turkarslan, David J. Reiss, Min Pan, June A. Burn, Kyle C. Costa, Thomas J. Lie, Joseph Slagel, Robert L. Moritz, Murray Hackett, John A. Leigh, Nitin S. Baliga

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1839-1851
Number of pages13
JournalGenome research
Issue number11
StatePublished - Nov 2013
Externally publishedYes


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