Transcription levels of a noncoding RNA orchestrate opposing regulatory and cell fate outcomes in yeast

Fabien Moretto,N Ezgi Wood,Minghao Chia,Cai Li,Nicholas M Luscombe,Folkert J Van Werven

doi:10.1016/j.celrep.2020.108643

Abstract

SummaryTranscription through noncoding regions of the genome is pervasive. How these transcription events regulate gene expression remains poorly understood. Here, we report that, in S. cerevisiae, the levels of transcription through a noncoding region, IRT2, located upstream in the promoter of the inducer of meiosis, IME1, regulate opposing chromatin and transcription states. At low levels, the act of IRT2 transcription promotes histone exchange, delivering acetylated histone H3 lysine 56 to chromatin locally. The subsequent open chromatin state directs transcription factor recruitment and induces downstream transcription to repress the IME1 promoter and meiotic entry. Conversely, increasing transcription turns IRT2 into a repressor by promoting transcription-coupled chromatin assembly. The two opposing functions of IRT2 transcription shape a regulatory circuit, which ensures a robust cell-type-specific control of IME1 expression and yeast meiosis. Our data illustrate how intergenic transcription levels are key to controlling local chromatin state, gene expression, and cell fate outcomes.

Highlights

Transcription in intergenic regions of the genome is widespread
IRT2 is required for repression of IME1 in cells with a single mating type We hypothesized that there is a mechanism to ensure a robust transition from nutrient to mating-type control of yeast meiosis, involving the two long noncoding RNAs (lncRNAs) expressed in the IME1 promoter
Two distinct IME1 regulating transcript 1 (IRT1) species were detected by northern blot, which were reduced to one truncated transcript when IRT1 transcription was terminated early (Figure 1B, lanes 7–10; Figure S1C)

Summary

Introduction

Transcription in intergenic regions of the genome is widespread. The noncoding RNAs emanating from these transcription events embody a large fraction of the transcriptome (Hon et al, 2017; Iyer et al, 2015; Kung et al, 2013). Noncoding transcription occurs near protein coding genes in promoter regions or at the 30 ends of genes where they produce sense or antisense lncRNA transcripts (Neil et al, 2009; Pelechano and Steinmetz, 2013; Tisseur et al, 2011; Xu et al, 2009). Noncoding transcription can locally regulate the expression of coding genes through various mechanisms (Gil and Ulitsky, 2020; Wang and Chang, 2011). A widespread mechanism by which noncoding regions regulate gene expression is through the act of transcription via RNA polymerase II (Pol II) (Kornienko et al, 2013). Pol II recruits chromatin remodelers that modify chromatin locally, thereby regulating the transcription of nearby genes (Ard et al, 2017; Venkatesh and Workman, 2015)

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