Emergence of essential functions of a transcription factor in the cyanobacterium Nostoc/Anabaena sp. PCC 7120 [ChIP-seq]

How new functions emerge as genes diversify during evolution is an important question in biology. cyclic adenosine monophosphate receptor protein (CRP) -type transcription factors are widespread in bacteria, often with several members coexisting in the same organism. How do they achieve functional specificity with highly conserved structures? In the filamentous cyanobacterium Nostoc/Anabaena sp. PCC 7120, both NtcA and DevH belong to the CRP family, yet DevH is essential while NtcA is not. Together with previously published data, we demonstrate here that ntcA and devH mutually and positively regulate each other for enhanced expression. Furthermore, NtcA and DevH share a common consensus DNA binding site, and both of them exert global regulation functions for metabolism, photosynthesis and cell development. We show that compared to NtcA, DevH achieved functional specificity and essentiality by structural innovations and increased cellular concentrations, leading to a stronger and broader regulatory function independent of allosteric control. Based on our data, we propose a model on how these two conserved transcription factors provide both overlapping and distinct regulatory functions, to better coordinate transcriptional activities under different conditions. This study constitutes an example illustrating how functional divergence can be achieved following gene diversification of transcription factors, leading to increased complexity in gene regulation networks. ChIP-seq of FLAG in the Anabaena devH-flag strain, in which the native devH was replaced by an allele encoding a DevH variant tagged with 3×FLAG at the C-terminus, and in the wild type strain as a control.