Maffioletti, A. | bioRxiv Science

bioRxiv2021

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

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.

molecular biology↗

bioRxiv2019

Fine chromatin-driven mechanism of transcription interference by antisense noncoding transcription

Eukaryotic genomes are almost entirely transcribed by RNA polymerase II (RNAPII). Consequently, the transcription of long noncoding RNAs (lncRNAs) often overlaps with coding gene promoters triggering potential gene repression through a poorly characterized mechanism of transcription interference. In this study, we propose a global model of chromatin-based transcription interference in Saccharomyces cerevisiae (S. cerevisiae). By using a noncoding transcription inducible strain, we analyzed the relationship between antisense elongation and coding sense repression, nucleosome occupancy and transcription-associated histone modifications using near-base pair resolution techniques. We show that antisense noncoding transcription leads to the deaceylation of a subpopulation of -1/+1 nucleosomes associated with increased H3K36 trimethylation (H3K36me3). Reduced acetylation results in decreased binding of the RSC chromatin remodeler at -1/+1 nucleosomes and subsequent sliding into the Nucleosome-Depleted Region (NDR) hindering Pre-Initiation Complex (PIC) association. Finally, we extend our model by showing that natural antisense noncoding transcription significantly represses around 20% of S. cerevisiae genes through this chromatin-based transcription interference mechanism.\n\nHighlightsO_LIInduction of antisense noncoding transcription leads to -1/+1 nucleosome sliding that competes with sense transcription PIC deposition.\nC_LIO_LIAntisense induction leads to a subpopulation of H3K36me3 nucleosomes differently positioned compared to H3K18ac nucleosomes.\nC_LIO_LIRSC chromatin remodeler recruitment to -1/+1 nucleosomes is modulated by histone acetylation levels.\nC_LIO_LI20% of S. cerevisiae genes are significantly repressed by this antisense-dependent chromatin-based transcription interference mechanism.\nC_LI

molecular biology↗