Chromatin- and Transcription-Related Factors Repress Transcription from within Coding Regions throughout the Saccharomyces cerevisiae Genome

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Abstract
Previous studies in Saccharomyces cerevisiae have demonstrated that cryptic promoters within coding regions activate transcription in particular mutants. We have performed a comprehensive analysis of cryptic transcription in order to identify factors that normally repress cryptic promoters, to determine the amount of cryptic transcription genome-wide, and to study the potential for expression of genetic information by cryptic transcription. Our results show that a large number of factors that control chromatin structure and transcription are required to repress cryptic transcription from at least 1,000 locations across the S. cerevisiae genome. Two results suggest that some cryptic transcripts are translated. First, as expected, many cryptic transcripts contain an ATG and an open reading frame of at least 100 codons. Second, several cryptic transcripts are translated into proteins. Furthermore, a subset of cryptic transcripts tested is transiently induced in wild-type cells following a nutritional shift, suggesting a possible physiological role in response to a change in growth conditions. Taken together, our results demonstrate that, during normal growth, the global integrity of gene expression is maintained by a wide range of factors and suggest that, under altered genetic or physiological conditions, the expression of alternative genetic information may occur. Recent studies have shown that much more of the eukaryotic genome is transcribed into RNA than previously thought. In Saccharomyces cerevisiae, when particular factors are defective, cryptic promoters within several coding regions become active and produce shorter transcripts corresponding to the 3′ portions of genes. (Transcription proceeds from the 5′ end of genes to the 3′ end.) A comprehensive analysis of cryptic transcription identified the factors that normally repress this event. We find that at least 50 factors, many involved in chromatin structure and transcription, are required to repress cryptic transcription. Other results suggest that the potential for cryptic transcription is widespread, initiating from at least 1,000 locations across the S. cerevisiae genome. In mutants in which cryptic transcripts are produced, some of the transcripts are translated into proteins not normally made in unmodified, wild-type cells. Finally, in wild-type cells, a subset of cryptic transcripts is transiently induced following a nutritional shift, suggesting a possible role for cryptic transcription. Taken together, our results demonstrate that the normal pattern of gene expression is maintained by a wide range of factors and suggest that, under altered genetic or physiological conditions, the expression of alternative genetic information may occur.