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 <i>Methylomonas</i> 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 <i>Methylomonas</i>. This study provides deeper insights into the transcriptional regulation strategies of methanotrophs under nitrogen-limited conditions.