HetR homodimer is a DNA-binding protein required for heterocyst differentiation, and the DNA-binding activity is inhibited by PatS

<jats:p> HetR plays a key role in regulation of heterocyst differentiation. When the Cys-48 residue of the HetR from <jats:italic>Anabaena</jats:italic> sp. PCC 7120 was replaced with an Ala residue, the mutant HetR (HetR <jats:sub>C48A</jats:sub> ) could not dimerize, indicating that HetR forms a homodimer through a disulfide bond. The <jats:italic>Anabaena</jats:italic> strain C48, containing the <jats:italic>hetRc48a</jats:italic> gene, could not produce HetR homodimer and failed to form heterocyst. We show that HetR is a DNA-binding protein and that its homodimerization is required for the DNA binding. HetR binds the promoter regions of <jats:italic>hetR</jats:italic> , <jats:italic>hepA</jats:italic> , and <jats:italic>patS</jats:italic> , suggesting a direct control of the expression of these genes by HetR. We present evidence that shows that the up-regulation of <jats:italic>patS</jats:italic> and <jats:italic>hetR</jats:italic> depends on DNA binding by HetR dimer. The pentapeptide RGSGR, which is present at the C terminus of PatS and blocks heterocyst formation, inhibits the DNA binding of HetR and prevents <jats:italic>hetR</jats:italic> up-regulation. </jats:p>