Title: "New insights into regulatory transcriptomics from next-generation sequencing"
Speaker: Christina Leslie; Computational Biology Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center

Place: Mechanical Engineering (ME) 1130
Date: March 5, 2013; Tuesday
Time: 4:30pm

Abstract: Many large-scale genomics projects, including the human ENCODE project, are using DNA-sequencing technologies like ChIP-seq and DNase-seq to comprehensively map the "epigenome" -- the cell-type specific state of the chromatin, including the genome-wide binding profiles of DNA-binding proteins, chromatin marks, and regions of open chromatin. These data tell us mainly about transcriptional regulation and not about subsequent regulatory steps. Now, emerging technologies based on RNA sequencing are beginning to shed light on co-transcriptional and post-transcriptional regulatory processes -- for example, regulation of RNA processing and gene silencing by microRNAs. We will describe our recent work in this new area of "regulatory transcriptomics" based on two new sequencing technologies: (1) CLIP-seq (cross-linking immunoprecipitation followed by next-generation sequencing) for mapping the transcriptome-wide binding sites of RNA-binding proteins; and (2) 3'-seq for mapping the alternative 3'-ends of all polyadenylated transcripts. We will describe how combining Argonaute CLIP-seq with a genetics approach ("differential CLIP-seq") defines, for the first time, the full set of targets of a single microRNA in a physiological context. This analysis reveals widespread non-canonical targeting, defining a wider range of sequence specificity patterns than previously known. We will also describe a new and quantitative 3'-seq method that we use to decipher tissue- and pathway-specific alternative cleavage and polyadenylation in human cells. We will introduce the necessary biological background and basics on next-generation sequencing technologies so that the talk will be accessible to an interdisciplinary audience.

Associated reading:
Loeb et al., (2012) Transcriptome-wide miR-155 Binding Map Reveals Widespread Noncanonical MicroRNA Targeting. Molecular Cell, Volume 48, Issue 5, 760-770.

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