Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5′ Promoters in Yeast

Rawal, Yashpal; Chereji, Răzvan V.; Valabhoju, Vishalini; Qiu, Hongfang; Ocampo, Josefina; Clark, David; Hinnebusch, Alan G.

doi:10.1016/j.molcel.2018.03.007

Cited by 56 publications

(117 citation statements)

References 58 publications

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“…2). Our observations are in agreement with recent reports that demonstrate how Gcn4 binds frequently in coding regions and can activate transcription from internal promoters (Rawal et al 2018;Mittal et al 2017). This suggests that a signigicant fraction of the cryptic promoters are in fact alternative promoters, whose expression under standard conditions is restricted by the chromatin organization or the absence of a particular transcription factor.…”

Section: Discussionsupporting

confidence: 93%

Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

Hennig²,

Wang

et al. 2018

Preprint

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Cryptic transcription is widespread and generates a heterogeneous group of RNA molecules of unknown function. To improve our understanding of cryptic transcription, we investigated their transcription start site usage, chromatin organization and post-transcriptional consequences in Saccharomyces cerevisiae. We show that transcription start sites (TSSs) of chromatin-sensitive internal cryptic transcripts retain comparable features of canonical TSSs in terms of DNA sequence, directionality and chromatin accessibility. We degine the 5' and 3' boundaries of cryptic transcripts and show that, contrary to RNA degradation-sensitive ones, they often overlap with the end of the gene thereby using the canonical polyadenylation site and associate to polyribosomes. We show that chromatin-sensitive cryptic transcripts can be recognized by ribosomes and may produce truncated polypeptides from downstream, in-frame start codons. Finally, we congirm the presence of the predicted polypeptides by reanalyzing N-terminal proteomic datasets. Our work suggests that a fraction of chromatin-sensitive internal cryptic promoters are in fact alternative truncated mRNA isoforms. The expression of these chromatin-sensitive isoforms is conserved from yeast to human expanding the functional consequences of cryptic transcription and proteome complexity.

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Section: Discussionsupporting

confidence: 93%

Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

Hennig²,

Wang

et al. 2018

Preprint

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“…However, not all intragenic promoters that have been identified are active in spt6-1004. For example, a recent study showed that Gcn4 activates transcription from many intragenic sites (Rawal et al, 2018) and most of those are not activated in an spt6-1004 mutant. In addition to encoding N-terminally truncated proteins, intragenic promoters can play other types of regulatory roles, such as interference with normal gene expression (Kim et al, 2017;Xie et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Spt6 is required for the fidelity of promoter selection

Doris

Chuang

Viktorovskaya

et al. 2018

Preprint

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4 Co-first authors 5 Lead contact running head: Spt6 regulates transcription initiation keywords: Spt6; transcription start sites; intragenic promoters; chromatin structure correspondence: winston@genetics.med.harvard.edu 2 SUMMARY Spt6 is a conserved factor that controls transcription and chromatin structure across the genome. Although Spt6 is viewed as an elongation factor, spt6 mutations in Saccharomyces cerevisiae allow elevated levels of transcripts from within coding regions, suggesting that Spt6 also controls initiation. To address the requirements for Spt6 in transcription and chromatin structure, we have combined four genome-wide approaches. Our results demonstrate that Spt6 represses transcription initiation at thousands of intragenic promoters. We characterize these intragenic promoters, and find sequence features conserved with genic promoters. Finally, we show that Spt6 also regulates transcription initiation at most genic promoters and propose a model of initiation-site competition to account for this. Together, our results demonstrate that Spt6 controls the fidelity of transcription initiation throughout the genome and reveal the magnitude of the potential for expressing alternative genetic information via intragenic promoters.3

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“…Promoter-proximal pausing of Pol II is common in higher eukaryotes, but it is not generally observed in yeast (Mayer et al 2017). In wild-type cells, Pol II levels are low at the promoter and high on the gene (elongating Pol II), with a well-resolved dip at the transcript termination site (TTS), and a peak just downstream from the TTS that sometimes trails into the next gene, corresponding to terminating Pol II (Cole et al 2014;Rawal et al 2018b). Pol II transcribes through the TTS, which refers to the mRNA cleavage site, where poly(A) is added and the mRNA is released.…”

Section: Rsc and Isw1/chd1 Have Opposite Effects On The Levels Of Elomentioning

confidence: 99%

Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination

et al. 2019

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Most yeast genes have a nucleosome-depleted region (NDR) at the promoter and an array of regularly spaced nucleosomes phased relative to the transcription start site. We have examined the interplay between RSC (a conserved essential SWI/SNFtype complex that determines NDR size) and the ISW1, CHD1, and ISW2 nucleosome spacing enzymes in chromatin organization and transcription, using isogenic strains lacking all combinations of these enzymes. The contributions of these remodelers to chromatin organization are largely combinatorial, distinct, and nonredundant, supporting a model in which the +1 nucleosome is positioned by RSC and then used as a reference nucleosome by the spacing enzymes. Defective chromatin organization correlates with altered RNA polymerase II (Pol II) distribution. RSC-depleted cells exhibit low levels of elongating Pol II and high levels of terminating Pol II, consistent with defects in both termination and initiation, suggesting that RSC facilitates both. Cells lacking both ISW1 and CHD1 show the opposite Pol II distribution, suggesting elongation and termination defects. These cells have extremely disrupted chromatin, with high levels of closely packed dinucleosomes involving the second (+2) nucleosome. We propose that ISW1 and CHD1 facilitate Pol II elongation by separating closely packed nucleosomes.

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Gcn4 Binding in Coding Regions Can Activate Internal and Canonical 5′ Promoters in Yeast

Cited by 56 publications

References 58 publications

Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

Chromatin-sensitive cryptic promoters encode alternative protein isoforms in yeast

Spt6 is required for the fidelity of promoter selection

Contrasting roles of the RSC and ISW1/CHD1 chromatin remodelers in RNA polymerase II elongation and termination

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