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Comprehensive profiling of the fission yeast transcription start site activity during stress and media response.

ABSTRACT: Fission yeast, Schizosaccharomyces pombe, is an attractive model organism for transcriptional and chromatin biology research. Such research is contingent of accurate annotation of genes and in particular Transcription Start Sites (TSSs) and thereby core promoters. However, comprehensive genome-wide maps of TSS and their usage across commonly applied laboratorial conditions and treatments for S. pombe are lacking. To this end, we have applied Cap Analysis of Gene Expression (CAGE) to profile TSSs activity in S. pombe cultures exposed to heat shock, nitrogen starvation, peroxide and two commonly applied media, YES and EMM. CAGE allows for nucleotide resolution detection of TSS, which we show is substantially more accurate than existing PomBase annotation. On gene expression levels, we recapitulate known S. pombe stress response patterns, but our data also allowed us to detect many alternative TSSs within gene bodies that are changing their activity between conditions. Some of these have the potential to change the functions of encoded proteins due to coding sequence exclusion. We show that the immediate region around TSSs is almost as conserved as coding sequence across S. pombe strains, but the upstream promoter which houses transcription factor binding sites linked to stress response show high diversity. Our data constitute a central resource for S. pombe transcriptional regulation research.

ORGANISM(S): Schizosaccharomyces pombe

PROVIDER: GSE110976 | GEO | 2018/03/14

REPOSITORIES: GEO

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Project description:More than half of human protein-coding genes have an alternative transcription start site (TSS). We aimed to investigate the contribution of alternative TSSs to the acute-stress–induced transcriptome response in human tissue (skeletal muscle) using the cap analysis of gene expression approach. TSSs were examined at baseline and during recovery after acute stress (a cycling exercise). We identified 44,680 CAGE TSS clusters (including 3,764 first defined) belonging to 12,268 genes and annotated for the first time 290 TSSs belonging to 163 genes. The transcriptome dynamically changes during the first hours after acute stress; the change in the expression of 10% of genes was associated with the activation of alternative TSSs, indicating differential TSSs usage. The majority of the alternative TSSs do not increase proteome complexity suggesting that the function of thousands of alternative TSSs is associated with the fine regulation of mRNA isoform expression from a gene due to the transcription factor-specific activation of various alternative TSSs. We identified individual muscle promoter regions for each TSS using muscle open chromatin data (ATAC-seq and DNase-seq). Then, using the positional weight matrix approach we predicted time course activation of “classic” transcription factors involved in response of skeletal muscle to contractile activity, as well as diversity of less/un-investigated factors. Transcriptome response induced by acute stress related to activation of the alternative TSSs indicates that differential TSSs usage is an essential mechanism of fine regulation of gene response to stress stimulus. A comprehensive resource of accurate TSSs and individual promoter regions for each TSS in muscle was created. This resource together with the positional weight matrix approach can be used to accurate prediction of TFs in any gene(s) of interest involved in the response to various stimuli, interventions or pathological conditions in human skeletal muscle.

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Comprehensive profiling of the fission yeast transcription start site activity during stress and media response.

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