Department of Biological Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Genes Dev. 2011 Jan 1;25(1):29-40. doi: 10.1101/gad.1975011. Epub 2010 Dec 14.
Transcription of non-protein-coding DNA (ncDNA) and its noncoding RNA (ncRNA) products are beginning to emerge as key regulators of gene expression. We previously identified a regulatory system in Saccharomyces cerevisiae whereby transcription of intergenic ncDNA (SRG1) represses transcription of an adjacent protein-coding gene (SER3) through transcription interference. We now provide evidence that SRG1 transcription causes repression of SER3 by directing a high level of nucleosomes over SRG1, which overlaps the SER3 promoter. Repression by SRG1 transcription is dependent on the Spt6 and Spt16 transcription elongation factors. Significantly, spt6 and spt16 mutations reduce nucleosome levels over the SER3 promoter without reducing intergenic SRG1 transcription, strongly suggesting that nucleosome levels, not transcription levels, cause SER3 repression. Finally, we show that spt6 and spt16 mutations allow transcription factor access to the SER3 promoter. Our results raise the possibility that transcription of ncDNA may contribute to nucleosome positioning on a genome-wide scale where, in some cases, it negatively impacts protein-DNA interactions.
非蛋白编码 DNA(ncDNA)及其非编码 RNA(ncRNA)产物的转录开始成为基因表达的关键调节剂。我们之前在酿酒酵母中鉴定了一个调控系统，其中通过转录干扰，基因间 ncDNA(SRG1)的转录抑制了相邻的蛋白质编码基因(SER3)的转录。现在我们提供的证据表明，SRG1 转录通过在重叠 SER3 启动子的位置上引导高水平的核小体来抑制 SER3 的转录。SRG1 转录的抑制依赖于 Spt6 和 Spt16 转录延伸因子。重要的是，spt6 和 spt16 突变降低了 SER3 启动子上的核小体水平，而不降低基因间的 SRG1 转录，这强烈表明核小体水平而不是转录水平导致 SER3 抑制。最后，我们表明 spt6 和 spt16 突变允许转录因子访问 SER3 启动子。我们的结果提出了这样一种可能性，即 ncDNA 的转录可能有助于在全基因组范围内形成核小体定位，在某些情况下，它会对蛋白质-DNA 相互作用产生负面影响。
