Local potentiation of stress-responsive genes by upstream noncoding transcription

Abstract

It has been postulated that a myriad of long noncoding RNAs (lncRNAs) contribute to gene regulation. In fission yeast, glucose starvation triggers lncRNA transcription across promoter regions of stress-responsive genes including fbp1 (fructose-1,6-bisphosphatase1). At the fbp1 promoter, this transcription promotes chromatin remodeling and fbp1 mRNA expression. Here, we demonstrate that such upstream noncoding transcription facilitates promoter association of the stress-responsive transcriptional activator Atf1 at the sites of transcription, leading to activation of the downstream stress genes. Genome-wide analyses revealed that ∼50 Atf1-binding sites show marked decrease in Atf1 occupancy when cells are treated with a transcription inhibitor. Most of these transcription-enhanced Atf1-binding sites are associated with stress-dependent induction of the adjacent mRNAs or lncRNAs, as observed in fbp1. These Atf1-binding sites exhibit low Atf1 occupancy and high histone density in glucose-rich conditions, and undergo dramatic changes in chromatin status after glucose depletion: enhanced Atf1 binding, histone eviction, and histone H3 acetylation. We also found that upstream transcripts bind to the Groucho-Tup1 type transcriptional corepressors Tup11 and Tup12, and locally antagonize their repressive functions on Atf1 binding. These results reveal a new mechanism in which upstream noncoding transcription locally magnifies the specific activation of stress-inducible genes via counteraction of corepressors.

RNA decay systems enhance reciprocal switching of sense and antisense transcripts in response to glucose starvation

“…; Takemata et al . ). This may interfere with transcription on the other strand, for example, via RNA pol II collision, or steric exclusion of transcriptional factors.…”

“…), and sense fbp1 mlonRNA transcripts promote transcription locally by antagonizing Tup11 and Tup12 repressors (Takemata et al . ). A stringent algorithm identified 9 other high‐confidence loci with fbp1‐ like mlonRNA transcription through the far upstream promoter region that were induced after glucose starvation.…”

Interplay between chromatin modulators and histone acetylation regulates the formation of accessible chromatin in the upstream regulatory region of fission yeast <i>fbp1</i>

“…The lncRNAs have been referred to as 'metabolic stress-induced long non-coding RNA (mlonRNA) (Galipon et al, 2013;Miki et al, 2016), and this mlonRNA transcription is involved in the chromatin opening and the binding of transcription activators at the fbp1 promoter (Hirota et al, 2008a;Takemata et al, 2016). Our recent study demonstrated that the mlonRNAs interact with Tup11/12 corepressors to antagonize the repressive function of Tup11/12 and thereby enhance binding of Atf1, which in turn induces histone acetylation through the recruitment of Gcn5 HAT (Takemata et al, 2016). Having established the functional link between mlonRNAs, transcription activators and histone acetylation, the roles played by ADCRs in these processes remain to be elucidated.…”

Transcription-coupled changes to chromatin underpin gene silencing by transcriptional interference

“…The act of intergenic lncRNA transcription can also have a profound impact on the expression of nearby genes. For example, the activation of the fbp1 + gene in fission yeast ( Schizosaccharomyces pombe ) occurs in response to glucose starvation and requires upstream lncRNA transcription to evict promoter-associated repressors and permit transcription factor binding (31,32). Conversely, a phenomenon known as ‘transcriptional interference’ often involves transcription of lncRNAs into downstream gene promoters to repress their expression.…”