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Bioinformatics reveals new gene regulation system

o genes are neighbors in many diverse genomes, then they are likely to be related." Indeed, the Nrd genes and the transcription factor genes clustered together, providing additional evidence that the regulatory picture drawn by the team was correct.

Israeli researchers simultaneously showed through 'wet' biology experiments in Streptomyces bacteria that a transcription factor from this family represses Nrd gene expression in the living bacterial cell, confirming the Russian researchers' predictions. Confident that they had identified a new repressor of bacterial genes, Gelfand and Rodionov searched genomes for other upstream sites where the NrdR-box occurred. They found that it regulates other genes related to DNA replication, such as the enzymes that cut, paste, and untangle new DNA as it is synthesized, and enzymes that are involved in recycling nucleotide building blocks.

Although the work does not have direct application to human medicine, Gelfand pointed out that many antibiotics work by attacking the process of bacterial DNA replication. So, he said, this work has identified potential targets for designing new antibiotic drugs. But more importantly, the work shows how molecular discoveries of whole regulatory systems can be made through careful analysis of genomes--without ever lifting a pipette, he said.

"There are 100 enzymes functioning at the core of bacterial metabolism for which the genes are still unknown," said Gelfand. Using multiple bioinformatics tools can uncover cell systems that might have escaped experimental detection, he suggested. "By comparing hundreds of genomes, you can see patterns that are not seen when looking at just a couple of them."


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Source:Howard Hughes Medical Institute


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