报告题目：Cis-regulatory roles of lncRNAs in transcription and stem cell differentiation
报告人：沈晓骅，教授；清华大学医学院、生命联合中心
报告时间：2017 年 3 月 31 日，上午 10:00-11:00
报告地点：生科院一楼中厅

Cis-regulatory roles of lncRNAs in transcription and stem cell differentiation

Pervasive transcription in mammalian genome produces thousands of long noncoding RNA (lncRNA) transcripts, which have been implicated in controlling various aspects of biology. However, the functions of specific lncRNAs, and the molecular mechanisms through which they act, remain unclear. RNA may represent a hidden layer of regulatory information in complex organisms. In the past years, we have rigorously investigated lncRNA functions and revealed two paradigms in lncRNA-mediated regulations of gene expression. First, we discovered a novel mode of transcription fine-tuning mechanism mediated by a lncRNA gene. While the DNA sequences of the lncRNA Haunt serve as enhancers to promotes the expression of its downstream HOXA genes, its RNA transcripts repress HOXA genes through its chromatin association. The opposing functions of the Haunt DNA and transcripts lead to fine-tuned expression of HOXAs and orchestrate ESC differentiation. Second, we revealed a prevalent mode of gene regulation by divergent lncRNAs on nearby transcription. Divergent lncRNAs, at least a subset of them, regulate nearby gene transcription and participate in similar developmental or biological processes known to involve in nearby protein-coding genes. From this point of view, the functionality of thousands of uncharacterized lncRNA genes can be rapidly predicted on the basis of the knowledge of their neighboring genes. Our work provide important conceptual as well as technical advances to understand the functionality and evolution of non-coding portions of the genome.
Selected publications:
1.Luo S, Lu J, Liu L, Yin Y, Han X, Xu R, Wu B, Liu W, Yan P, Shao W, Chen C, Lu Z, Na J, Tang F, Wang J, Zhang Y.E. and Shen X. (2016). Divergent lncRNAs regulate gene expression and lineage differentiation in pluripotent cells. Cell Stem Cell. 18(5):637-52.
2.Yin Y, Yan P, Lu J, Song G, Zhu Y, Li Z, Zhao Y, Shen B, Huang X, Zhu H, Orkin SH, Shen X. (2015). Opposing roles for the lncRNA Haunt and its genomic locus in regulating HOXA gene activation during embryonic stem cell differentiation. Cell Stem Cell. 16(5):504-16.

沈晓骅，博士、研究员
清华大学医学院、生命联合中心
　　本科和博士分别毕业于南开大学和美国密歇根大学，哈佛大学医学院和Dana-Farber 癌症研究所做博士后和讲师，2010年底入职清华大学，2016年获tenure。曾任973首席科学家获，获求是杰出青年奖等。沈晓骅有较大跨度的科研经历，曾利用多种模式生物进行多项原创性研究，包括最早建立C. elegans模型研究未折叠蛋白信号传导 (Cell, 2001)，构建并揭示了一个以表观遗传因子为中心的蛋白互联网对干细胞多能性的重要调控作用 (Mol Cell, 2008; Cell, 2009)。沈晓骅实验室目前主要以胚胎干细胞为模型，进行长链非编码RNA（lncRNA）的生物学功能研究，揭示了lncRNA介导基因表达调控的新模式和规律，并阐明其在干细胞分化中的重要作用 (Cell Stem Cell. 2015 & 2016)。