Dept. of Molecular and Cellular Biology, University of Geneva, 1211 Geneva 4, Switzerland.
Nucleic Acids Res. 2022 May 6;50(8):4515-4528. doi: 10.1093/nar/gkac264.
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, 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.
真核生物基因组被 RNA 聚合酶 II（RNAPII）广泛转录，长非编码 RNA 的转录经常与编码基因启动子重叠。这可能导致一种名为转录干扰（TI）的编码基因抑制。在酿酒酵母中，TI 主要由反义非编码转录驱动，并通过启动子核小体耗竭区（NDR）的重塑发生。在这项研究中，我们开发了一种遗传筛选方法来鉴定参与反义介导转录干扰（AMTI）的新参与者。在候选者中，我们发现了已知参与从头组蛋白沉积的 HIR 组蛋白伴侣复合物。使用全基因组方法，我们揭示了 HIR 依赖性组蛋白沉积通过反义非编码转录抑制 SAGA 依赖性基因的启动子。然而，尽管反义转录在 SAGA 依赖性基因的启动子上富集，但这一特征不足以定义基因调控的模式。我们进一步表明，启动子处 HIR 依赖性核小体掺入和转录因子结合之间的平衡将转录导向 SAGA 或 TFIID 依赖性调控。这项研究揭示了反义非编码转录与编码转录起始性质之间的新联系。
