Coordination of N₂-fixing cell specialization and patterning in filamentous cyanobacteria by a uniquely structured σ...

Cell differentiation and Turing-like patterning are tightly associated in a group of filamentous cyanobacteria that differentiate specialized N₂-fixing cells, called heterocysts. Based on systematic genetic analyses, in particular genome-wide identification of recognized promoters and assays with a reconstituted Anabaena transcription system in Escherichia coli, we established HetZ as the central activator of the gene regulatory network of heterocyst differentiation. Biochemical and cryo-EM analyses further established HetZ as a σ factor (σ^HetZ). Unique domain insertions in σ^HetZ are involved in promoter DNA recognition-unwinding and interaction with the inhibitor PatU3. σ^HetZ-PatU3 and the master regulator-diffusible inhibitor constitute the minimal core regulatory circuit (CRC) for cell fate determination and patterning. σ^HetZ activates not only genes of the CRC but also downstream regulator/effector genes involved in morphological and functional development. The gene regulatory network and the structure-function relationship of σ^HetZ depict how cell differentiation and patterning are coordinated in this group of multicellular cyanobacteria.