An evolutionarily conserved function of tRNA genes in genome organization.

摘要

The genomes of eukaryotic organisms are composed of regions with opposing transcriptional potential and structural properties. The precise maintenance of these heterochromatic and euchromatic domains, and proper management of regulatory elements within these domains, is critical for proper development and differentiation. Maintenance of these domains is mediated in part by DNA elements called insulators which restrict regulatory elements in one domain from acting on elements in a separate domain. Insulators are defined by their ability to either block the spread of repressive chromatin into more active regions or by their ability to disrupt enhancer mediated gene activation. Previous work in yeast has found tRNA genes are able to block the effect of silencer elements from encroaching on the active surrounding DNA. In this work I identify proteins involved in this process in yeast using a screen of all non-essential yeast proteins. I extend these results to human cells were I find tRNA genes also mediate the antagonism of repressed chromatin domains and block enhancer mediated gene activation, a function not previously ascribed to tRNA genes. Human tRNA genes exist in a chromatin environment characteristic of previously described insulators. This suggests a striking conservation of function for tRNA genes and makes them the only insulator conserved over such a large evolutionary time frame.