Understanding How Transcription Factors with Metallic Cofactors Contribute to Regulation of Gene Expression

Transcription is the process of rewriting a stretch of DNA, called a gene, into RNA, which is then translated into a protein. Most organisms contain thousands of genes that each produce a unique protein with a specific function. The question is then raised, what would happen if every gene were producing every protein, all the time? The answer is self-destruction. So, there must be a way to regulate genes – an off or on switch. Transcription factors act as that switch. Transcription factors are proteins that bind to a specific DNA sequence to help activate or repress nearby genes. Transcription factors recognize and react to stressors in their environment to know when to bind or release from DNA. The DtxR, or diphtheria toxin repressor, family of transcription factors provide a prime example of eliciting a genomic response to environmental stresses. Typically, DtxR members bind a regulatory metal cofactor, often manganese or iron, to localize to DNA and repress the expression of genes involved in the uptake of their regulatory metal. In this study, we identified a genomic DNA-binding sequence for the DtxR transcription factor from the model organism Thermus thermophilus HB8. The DNA sequence identified was found in close proximity to a gene encoding for a manganese-dependent transporter (TTHA1941). By developing a novel, in vitro transcription assay, we showed that Thermus thermophilus HB8 DtxR represses TTHA1941 and that repression is dependent on manganese availability