Pervasive and dynamic transcription initiation in Saccharomyces cerevisiae

Abstract

Transcription initiation is finely regulated to ensure proper expression and function of genes. The regulated transcription initiation in response to various environmental stimuli in a classic model organism Saccharomyces cerevisiae has not been systematically investigated. In this study, we generated quantitative maps of transcription start sites (TSSs) at a single-nucleotide resolution for S. cerevisiae grown in nine different conditions using no-amplification nontagging Cap analysis of gene expression (nAnT-iCAGE) sequencing. We mapped ∼1 million well-supported TSSs, suggesting highly pervasive transcription initiation in the compact genome of the budding yeast. The comprehensive TSS maps allowed us to identify core promoters for ∼96% verified protein-coding genes. We corrected misannotation of translation start codon for 122 genes and suggested an alternative start codon for 57 genes. We found that 56% of yeast genes are controlled by multiple core promoters, and alternative core promoter usage by a gene is widespread in response to changing environments. Most core promoter shifts are coupled with altered gene expression, indicating that alternative core promoter usage might play an important role in controlling gene transcriptional activities. Based on their activities in responding to environmental cues, we divided core promoters into constitutive class (55%) and inducible class (45%). The two classes of core promoters display distinctive patterns in transcriptional abundance, chromatin structure, promoter shape, and sequence context. In summary, our study improved the annotation of the yeast genome and demonstrated a much more pervasive and dynamic nature of transcription initiation in yeast than previously recognized.

Hi-D: nanoscale mapping of nuclear dynamics in single living cells

“…We believe therefore that increased chromatin mobility upon serum starvation correlates with PIC breakdown. Conversely, when serum is present in the medium, activity of RNA Pol II and of PIC enzymes is restored and PIC will assemble onto DNA, both pervasively across the genome at background levels (pervasive transcription) and more stably at genes [53,54]. Reduced mobility of chromatin in the presence of serum suggests that stable PIC binding may serve as an anchoring function for individual chromatin fibers, on top of its essential function in transcription initiation.…”

So close, no matter how far: multiple paths connecting transcription to mRNA translation in eukaryotes

“…Intriguingly, these numbers are very similar to the estimated occurrence of AP in humans, despite the vast differences in their genomes. The authors found that as many as 85% of the genes possessing multiple promoters exhibited significant shifts of promoter activity in at least one of the nine tested conditions (Lu & Lin, 2019). Such a condition-dependent use of APs indicates that it might support differential gene expression, providing an additional layer of regulation (Ayoubi & Van De Yen, 1996).…”

“…Interestingly, this number is dramatically elevated following energy stress, suggesting condition-specific regulation (Tamarkin-Ben-Harush et al, 2017). A recently published work employed an improved CAGE technique to map, at the nucleotide resolution, hundreds of thousands of TSSs in the yeast Saccharomyces cerevisiae (Lu & Lin, 2019). The authors found that 56% of the expressed protein-coding genes employ alternative promoters when exposed to changing environmental conditions.…”

Epigenetic regulation of spurious transcription initiation in Arabidopsis

“…The development of high resolution 5 0 end-centered expression profiling techniques, such as oligo-capping methods 18 or cap analysis of gene expression (CAGE) 19 , has greatly advanced our understanding of gene regulation at a transcription initiation level. Studies employing these techniques have revealed both common and distinct features of the core promoters and their origin and regulation, in many organisms [20][21][22] . In mammals, for example, CAGE sequencing (CAGE-seq) analyses revealed that a large fraction of cell-type specific transcripts in stem and cancer cells originate from long terminal repeats (LTRs) of retroelements 23,24 .…”