Chromatin regulation by lncRNA

我们以前发现了一个参与裂解酵母FBP1基因染色质和基因调控的lncRNA。这种lncRNA(mLonRNA，代谢应激诱导的lncRNA)是从FBP1基因的远上游转录而来的，与编码片段重叠。作为对葡萄糖饥饿的响应，mLonRNAs的级联转录导致FBP1启动子染色质的逐步重塑，随后大量的mRNA被诱导。我们揭示了组蛋白的修饰是由mLonRNA转录和一些染色质修饰蛋白局部调控的。MLonRNA转录增强了atf1的染色质结合，从而形成了一个正反馈环。我们还发现mLonRNA被转运到细胞质中与多聚体结合。由于mLonRNA含有许多uORF，因此mLonRNA具有不小的编码潜力。RNA序列分析显示42个mLonRNA样lncRNAs和反义lncRNAs。我们还在小鼠培养的细胞中检测到mLonRNA样lncRNA。

We previously identified a lncRNA involved in chromatin and gene regulation of fission yeast fbp1 gene. This lncRNA (mlonRNA, metabolic stress induced lncRNA) is transcribed from the far upstream of fbp1 gene overlapping with the coding segment. In response to glucose starvation, cascade transcription of mlonRNAs occur to cause stepwise chromatin remodeling in the fbp1 promoter, followed by massive induction of mRNA.We here revealed histone modification is locally modulated by mlonRNA transcription and some chromatin modifying proteins. Chromatin binding of Atf1, which is necessary for mlonRNA transcription, is enhanced by mlonRNA transcription, thereby forming a positive feedback loop. We also discovered that mlonRNA is transported into cytoplasms to bind polysomes. Since mlonRNA harbors many uORFs, mlonRNA does not have little coding potential. RNA Seq analysis revealed 42 mlonRNA-like lncRNAs as well as antisense lncRNAs. We also detected mlonRNA-like lncRNA in mice cultured cells.