Genome-wide regulon of NtrC reveals genetic regulation under nitrogen limitation in Methylomonas sp. DH-1

Nitrogen is an essential element, but its scarcity often leads to growth constraints, driving the development of metabolic pathways and regulatory mechanisms. Here, we employed an integrated multi-omics approach to analyze the transcription factor NtrC and its regulon, elucidating the transcriptional adaptive response of Methylomonas sp. DH-1 to nitrogen limitation. An integrative analysis of ChIP-exo and RNA-seq revealed that 19 genes are directly regulated by NtrC. The NtrC regulon includes genes for glutamine synthesis, nitrite reduction, and formate/nitrite transport, suggesting a role in nitrogen assimilation. In-depth analysis revealed that various nitrogen metabolic pathways are regulated to coordinate with NtrC's role by increasing flux to ammonium. Additionally, pan-genome analysis confirmed that glutamine synthesis and nitrite metabolism are conserved as primary functions of NtrC within the genus Methylomonas. This study provides deeper insights into the transcriptional regulation strategies of methanotrophs under nitrogen-limited conditions.