The study describes the use of a Cas9 nuclease mutant, referred to as 'dead' Cas9 (dCas9), to engineer a programmable transcription regulator. dCas9 retains DNA-binding activity but lacks nuclease activity, allowing it to be directed to specific promoter regions or open reading frames (ORFs) to control gene expression. In *Escherichia coli*, dCas9 can be used as a transcription repressor by preventing RNA polymerase (RNAP) binding to promoters or as a transcription terminator by blocking RNAP elongation. In *Streptococcus pneumoniae*, dCas9 can repress gene expression by targeting ORFs. Additionally, dCas9 can be fused to the omega subunit of RNAP to achieve transcription activation. This technology provides a simple and efficient method for global regulation of gene expression, facilitating the study of gene networks and synthetic biology applications. The study also explores the modulation of dCas9-mediated repression levels through the introduction of mismatches in the crRNA guide sequence and demonstrates that wild-type Cas9 can repress gene expression in the presence of mismatches. Finally, the authors show that dCas9 can be used to activate gene expression by recruiting RNAP to promoter regions, with activation levels depending on the distance between the dCas9-binding site and the promoter.The study describes the use of a Cas9 nuclease mutant, referred to as 'dead' Cas9 (dCas9), to engineer a programmable transcription regulator. dCas9 retains DNA-binding activity but lacks nuclease activity, allowing it to be directed to specific promoter regions or open reading frames (ORFs) to control gene expression. In *Escherichia coli*, dCas9 can be used as a transcription repressor by preventing RNA polymerase (RNAP) binding to promoters or as a transcription terminator by blocking RNAP elongation. In *Streptococcus pneumoniae*, dCas9 can repress gene expression by targeting ORFs. Additionally, dCas9 can be fused to the omega subunit of RNAP to achieve transcription activation. This technology provides a simple and efficient method for global regulation of gene expression, facilitating the study of gene networks and synthetic biology applications. The study also explores the modulation of dCas9-mediated repression levels through the introduction of mismatches in the crRNA guide sequence and demonstrates that wild-type Cas9 can repress gene expression in the presence of mismatches. Finally, the authors show that dCas9 can be used to activate gene expression by recruiting RNAP to promoter regions, with activation levels depending on the distance between the dCas9-binding site and the promoter.