Expression from DIF1-motif promoters of hetR and patS is dependent on HetZ and modulated by PatU3 during heterocyst differentiation.

HetR and PatS/PatX-derived peptides are the activator and diffusible inhibitor for cell differentiation and patterning in heterocyst-forming cyanobacteria. HetR regulates target genes via HetR-recognition sites. However, some genes (such as patS/patX) upregulated at the early stage of heterocyst differentiation possess DIF1 (or DIF+) motif (TCCGGA) promoters rather than HetR-recognition sites; hetR possesses both predicted regulatory elements. How HetR controls heterocyst-specific expression from DIF1 motif promoters remains to be answered. This study presents evidence that the expression from DIF1 motif promoters of hetR, patS and patX is more directly dependent on hetZ, a gene regulated by HetR via a HetR-recognition site. The HetR-binding site upstream of hetR is not required for the autoregulation of hetR. PatU3 (3' portion of PatU) that interacts with HetZ may modulate the expression of hetR, hetZ and patS. These findings contribute to understanding of the mutual regulation of hetR, hetZ-patU and patS/patX in a large group of multicellular cyanobacteria.