Most proteins in trypanosomes, protozoan parasites that cause sleeping sickness and Chagas disease, are transcribed from just a few transcription initiation sites, meaning the resulting mRNA must be chopped into mRNAs for individual proteins. A new study published today (April 4) in Open Biology shows that rather than being regulated post-transcriptionally, gene expression is regulated by genome organization. Specifically, the distance of the genes from the nearest transcription initiation site appears to be related their levels of expression.
To study gene expression changes, scientists at the Universities of Oxford and Cambridge examined 777 genes whose expression changed during a heat shock challenge, which results in increased expression of a suite of proteins that help regulate proper protein conformation and prevent aggregation. The researchers then compared these expression changes to the genes’ distances from transcription initiation sites, and found that a large percentage of down-regulated genes, 36 percent, were within 20 kilobases of transcription initiation, while only 3 percent of upregulated genes were this close. Upregulated genes tended to be much farther away—more than 120 kb.
To test this, a neomycin resistance reporter gene was inserted at 8 kb and 284 kb away from a transcription initiation site. Sure enough, after heat shock, expression of the gene at 8 kb was lower than the gene at 284 kb from transcription initiation.
This relationship between gene expression and distance from transcription initiation provides evidence that “a major component of temporal gene-expression regulation in trypanosomes is achieved through spatial organization,” write the authors.