Antisense-mediated repression of SAGA-dependent genes involves the HIR histone chaperone

Abstract

Eukaryotic genomes are pervasively transcribed by RNA polymerase II (RNAPII), and transcription of long non-coding RNAs often overlaps with coding gene promoters. This might lead to coding gene repression in a process named Transcription Interference (TI). In Saccharomyces cerevisiae (S. cerevisiae), TI is mainly driven by antisense non-coding transcription and occurs through re-shaping of promoter Nucleosome-Depleted Regions (NDRs). In this study, we developed a genetic screen to identify new players involved in Antisense-Mediated Transcription Interference (AMTI). Among the candidates, we found the HIR histone chaperone complex known to be involved in de novo histone deposition. Using genome-wide approaches, we reveal that HIR-dependent histone deposition represses the promoters of SAGA-dependent genes via antisense non-coding transcription. However, while antisense transcription is enriched at promoters of SAGA-dependent genes, this feature is not sufficient to define the mode of gene regulation. We further show that the balance between HIR-dependent nucleosome incorporation and transcription factor binding at promoters directs transcription into a SAGA- or TFIID-dependent regulation. This study sheds light on a new connection between antisense non-coding transcription and the nature of coding transcription initiation.

Antisense non-coding transcription represses the PHO5 model gene at the level of promoter chromatin structure

“…In such culture conditions, the Pho4 transcriptional activator is rarely located in the nucleus (18). Thus, as we proposed in (42) for the SAGA-dependent gene class to which PHO5 belongs, the steady-state chromatin structure of the promoter NDR might be maintained tightly closed by ongoing AS transcription.…”

“…In such culture conditions, the Pho4 transcriptional activator is rarely located in the nucleus (18). Thus, as we proposed in (44) for the SAGA-dependent gene class to which PHO5 belongs, the steady-state chromatin structure of the promoter NDR might be maintained tightly closed by ongoing AS transcription. What may also be relevant to this mechanism is the recently discovered autoregulatory mechanism of the SAGA complex, which is induced in response to environmental changes such as phosphate starvation conditions (65).…”

“…The right panel represents RNAPII PAR-CLIP signal or nascent transcription signal in the same conditions. Data were retrieved from (42) and (43), respectively. (C) Levels of PHO5 mRNA in wild-type BMA41 (wt) and corresponding rrp6Δ mutant cells upon induction through phosphate starvation.…”

“…For RNA-seq and RNAPII PAR-CLIP, data were retrieved from (44) (GEO: GSE175991) and from (45) (GEO: GSE56435). Data of MNase-seq, ATAC-seq and Sth1 ChEC-seq were reanalyzed from (12) (GEO: GSE130946).…”