Conserved principles of transcriptional networks controlling metabolic flexibility in archaea

Gene regulation is intimately connected with metabolism, enabling the appropriate timing and tuning of biochemical pathways to substrate availability. In microorganisms, such as archaea and bacteria, transcription factors (TFs) often directly sense external cues such as nutrient substrates, metabolic intermediates, or redox status to regulate gene expression. Intense recent interest has characterized the functions of a large number of such regulatory TFs in archaea, which regulate a diverse array of unique archaeal metabolic capabilities. However, it remains unclear how the co-ordinated activity of the interconnected metabolic and transcription networks produces the dynamic flexibility so frequently observed in archaeal cells as they respond to energy limitation and intermittent substrate availability. In this review, we communicate the current state of the art regarding these archaeal networks and their dynamic properties. We compare the topology of these archaeal networks to those known for bacteria to highlight conserved and unique aspects. We present a new computational model for an exemplar archaeal network, aiming to lay the groundwork toward understanding general principles that unify the dynamic function of integrated metabolic-transcription networks across archaea and bacteria.