Cyanobacteria are the only prokaryotes performing oxygenic photosynthesis. Some filamentous cyanobacteria are capable of heterocyst differentiation to fix and assimilate atmospheric nitrogen when combined nitrogen sources are limited in the environment. Transcription factors that regulate gene expression play a crucial role in adapting to changing environments.

NtcA, belonging to the cAMP receptor protein (CRP) family, has been well-characterized as a global transcription factor. Despite its pleiotropic and global regulatory capabilities, NtcA is not essential for cyanobacterial survival. DevH, as another CRP family transcription factor, is poorly studied, and its function remains unknown.

In a recent study published in Cell Reports, a research group led by Prof. ZHANG Chengcai from the Institute of Hydrobiology (IHB) of the Chinese Academy of Sciences revealed the comprehensively characterized function of DevH and its interesting interplay with NtcA, which indicates the involvement of DevH in cell morphogenesis. 

Prof. ZHANG's group has long been dedicated to basic research on prokaryotic cell morphogenesis and environmental adaptation, as well as synthetic biology research related to cyanobacterial biotechnology and the control of cyanobacterial bloom. 

In this study, researchers demonstrated that the devH gene is essential for cyanobacterial survival under various conditions. They showed that DevH influences heterocyst differentiation starting from the early stage, rather than only affecting late-stage maturation as previously reported. 

By identifying the direct regulon by DevH, researchers elucidated the mechanism underlying the essentiality of DevH. They showed that it directly regulates various key physiological processes like photosynthesis, carbon-nitrogen metabolism, and the cell cycle. They identified the conserved DNA-binding motif recognized and bound by DevH to be highly similar to the one for NtcA. 

These findings showed that DevH and NtcA exhibit substantial functional overlap. One is essential for survival, while the other is only essential under specific conditions, suggesting inherent functional specificities. Researchers then explored how DevH demonstrates its essentiality by studying their auto-regulatory and cross-regulatory patterns, intracellular protein levels, structural differences, and phylogenetic evolutionary relationships. 

They found that during evolution, compared with NtcA, DevH in Anabaena develops distinct auto-regulatory patterns, shows significantly higher protein levels, and undergoes functionally meaningful changes in protein structure such as the acquisition of a positively charged E-loop and the loss of the binding pocket for the small molecule α-ketoglutarate. These characteristics enhance DevH's functions, making it an essential transcription factor for cells.

This study suggests that the cooperative interaction between transcription factors of the same family may represent a key physiological mechanism enabling cyanobacteria to maintain cell growth and survival in dynamically changing environments. It provides a paradigm for exploring functional emergence during evolutionary processes.