Department of Chemistry, Graduate School of Science, Tokyo Metropolitan University, Minamiosawa 1-1, Hachioji-shi, Tokyo, 192-0397, Japan.
Biology Department, Boston College, Chestnut Hill, MA, 02467, USA.
Sci Rep. 2019 Jan 22;9(1):299. doi: 10.1038/s41598-018-36049-0.
Long noncoding RNAs (lncRNAs) transcribed across gene promoters have been detected. These regulate transcription by mechanisms that have not been fully elucidated. We herein show that the chromatin configuration is altered into an accessible state within 290 bp downstream from the initiation site of metabolic-stress-induced lncRNAs (mlonRNAs) in the promoter of the fission yeast fbp1 gene, whose transcription is massively induced upon glucose starvation. Chromatin upstream from fbp1 is progressively altered into an open configuration, as a cascade of transcription of three overlapping mlonRNA species (-a, -b and -c in order) occurs with transcriptional initiation sites progressing 5' to 3' upstream of the fbp1 promoter. Initiation of the shortest mlonRNA (mlonRNA-c) induces chromatin remodeling around a transcription factor-binding site and subsequent massive induction of fbp1. We identify the cis-element required for mlonRNA-c initiation, and by changing the distance between mlonRNA-initiation site and the transcription factor-binding site, we show that mlonRNA-initiation effectively induces chromatin remodeling in a limited distance within 290 bp. These results indicate that mlonRNAs are transcribed across the fbp1 promoter as a short-range inducer for local chromatin alterations, and suggest that strict chromatin modulation is archived via stepwise mlonRNA-initiations.
长链非编码 RNA（lncRNA）可跨越基因启动子转录。这些 RNA 通过尚未完全阐明的机制来调节转录。我们在此表明，在有丝分裂酵母 fbp1 基因启动子中，代谢应激诱导的长非编码 RNA（mlonRNA）起始位点下游 290bp 范围内，染色质构象会改变为可及状态，该基因的转录在葡萄糖饥饿时会被大量诱导。fbp1 上游的染色质会逐渐改变为开放构象，因为三个重叠的 mlonRNA 种（-a、-b 和 -c）的转录级联发生，转录起始位点从 fbp1 启动子的 5' 端逐渐向 3' 端推进。最短的 mlonRNA（mlonRNA-c）的起始会诱导转录因子结合位点周围的染色质重塑，随后 fbp1 会被大量诱导。我们确定了 mlonRNA-c 起始所需的顺式元件，并通过改变 mlonRNA 起始位点和转录因子结合位点之间的距离，表明 mlonRNA 起始可以在 290bp 的有限距离内有效地诱导染色质重塑。这些结果表明，mlonRNAs 作为局部染色质改变的短程诱导物跨越 fbp1 启动子转录，并提示通过逐步的 mlonRNA 起始来实现严格的染色质调节。
