Project description:This SuperSeries is composed of the following subset Series: GSE23968: Large intergenic non-coding RNAs as novel modulators of reprogramming: ESCs, fibroblast, and fibroblast-derived iPSC (gene expression) GSE23970: Large intergenic non-coding RNAs as novel modulators of reprogramming: human embryonic stem cells, CD34+ cells, and CD34+ derived induced pluripotent stem cells (LincRNA expression) GSE23973: Large intergenic non-coding RNAs as novel modulators of reprogramming: siRNA (gene expression) GSE24181: Large intergenic non-coding RNAs as novel modulators of reprogramming: human embryonic stem cells, fibroblasts, and fibroblast-derived induced pluripotent stem cells (LincRNA expression) Refer to individual Series
Project description:We recently showed that the mammalian genome encodes more than a thousand large intergenic non-coding RNAs (lincRNAs) that are clearly conserved across mammals and thus functional. Gene expression patterns have implicated these lincRNAs in diverse biological processes including cell cycle regulation, immune surveillance, and embryonic stem cell pluripotency. However, the mechanism by which these lincRNAs function is unknown. Here, we expand the catalog of human lincRNAs to ~3300 by analyzing chromatin-state maps of various human cell types. Inspired by the observation that the well-characterized lincRNA HOTAIR bind the Polycomb Repressive Complex 2 (PRC2), we tested whether many lincRNAs are physically associated with PRC2. Remarkably, we observe that ~20% of lincRNAs expressed in various cell types are bound by PRC2, and that additional lincRNAs are bound by other chromatin-modifying complexes. Moreover, we show that siRNA-mediated depletion of certain lincRNAs associated with PRC2 leads to changes in gene expression and that the upregulated genes are enriched for those normally silenced by PRC2. We propose a model in which some lincRNAs guide chromatin–modifying complexes to specific genomic loci to regulate gene expression.
Project description:Many RNAs associate with chromatin, either directly or indirectly. To investigate the function of these RNAs, many technologies for mapping regions where RNAs interact across the genome have been developed. Adding information on the proteins involved in these RNA–chromatin interactions is critical for further analysis. Here, we developed RADIP (RNA and DNA interacting complexes ligated and sequenced (RADICL-seq) with immunoprecipitation), a novel technology that combines RADICL-seq technology with chromatin immunoprecipitation to characterize RNA–chromatin interactions mediated by individual proteins. We applied an anti-H3K27me3 antibody to the RADIP technology and generated libraries from mouse embryonic stem cells. We identified various RNAs, including protein-coding RNAs and non-coding RNAs, that were associated with chromatin via H3K27me3 mediation and that may facilitate the spread of Polycomb repressive complexes over broad regions of the mammalian genome.
Project description:Interventions: Case series:Nil
Primary outcome(s): intestinal microecological disorders;blood non-coding RNAs and immune status
Study Design: Randomized parallel controlled trial
Project description:In this study we predict functionally important long intergenic non-coding RNAs (lincRNAs) with a role in core essential processes in human. One of the candidate lincRNA, AC093323.3, was experimentally verified to affect cell viability. We performed RNASeq on knockdown of AC093323.3 to further investigate the functional role of this lincRNA.
