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101699 |
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|a dc
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|a Gurtan, Allan M.
|e author
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|a Massachusetts Institute of Technology. Department of Biological Engineering
|e contributor
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|a Massachusetts Institute of Technology. Department of Biology
|e contributor
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|a Koch Institute for Integrative Cancer Research at MIT
|e contributor
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1 |
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|a Gosline, Sara Jane Calafell
|e contributor
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1 |
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|a Gurtan, Allan M.
|e contributor
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|a JnBaptiste, Courtney K.
|e contributor
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1 |
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|a Bosson, Andrew
|e contributor
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1 |
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|a Milani, Pamela
|e contributor
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1 |
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|a Dalin, Simona Sara
|e contributor
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1 |
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|a Matthews, Bryan J.
|e contributor
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|a Yap, Yoon S.
|e contributor
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1 |
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|a Sharp, Phillip A.
|e contributor
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|a Fraenkel, Ernest
|e contributor
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|a JnBaptiste, Courtney K.
|e author
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| 700 |
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|a Bosson, Andrew
|e author
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| 700 |
1 |
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|a Milani, Pamela
|e author
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| 700 |
1 |
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|a Matthews, Bryan J.
|e author
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| 700 |
1 |
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|a Yap, Yoon S.
|e author
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| 700 |
1 |
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|a Sharp, Phillip A.
|e author
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| 700 |
1 |
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|a Fraenkel, Ernest
|e author
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| 700 |
1 |
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|a Gosline, Sara Jane Calafell
|e author
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| 700 |
1 |
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|a Gurtan, Allan M.
|e author
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| 700 |
1 |
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|a Sharp, Phillip A.
|e author
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| 700 |
1 |
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|a Dalin, Simona
|e author
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| 700 |
1 |
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|a JnBaptiste, Courtney Kenneil
|e author
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| 700 |
1 |
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|a Matthews, Bryan
|e author
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| 700 |
1 |
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|a Yap, Yoon Sing
|e author
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| 245 |
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|a Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements
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| 260 |
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|b Elsevier,
|c 2016-03-14T17:44:54Z.
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| 856 |
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|z Get fulltext
|u http://hdl.handle.net/1721.1/101699
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| 520 |
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|a MicroRNAs (miRNAs) regulate diverse biological processes by repressing mRNAs, but their modest effects on direct targets, together with their participation in larger regulatory networks, make it challenging to delineate miRNA-mediated effects. Here, we describe an approach to characterizing miRNA-regulatory networks by systematically profiling transcriptional, post-transcriptional and epigenetic activity in a pair of isogenic murine fibroblast cell lines with and without Dicer expression. By RNA sequencing (RNA-seq) and CLIP (crosslinking followed by immunoprecipitation) sequencing (CLIP-seq), we found that most of the changes induced by global miRNA loss occur at the level of transcription. We then introduced a network modeling approach that integrated these data with epigenetic data to identify specific miRNA-regulated transcription factors that explain the impact of miRNA perturbation on gene expression. In total, we demonstrate that combining multiple genome-wide datasets spanning diverse regulatory modes enables accurate delineation of the downstream miRNA-regulated transcriptional network and establishes a model for studying similar networks in other systems.
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| 520 |
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|a National Institutes of Health (U.S.) (Grant U54-CA112967)
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| 520 |
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|a National Institutes of Health (U.S.) (Grant R01-GM089903)
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| 520 |
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|a National Institutes of Health (U.S.) (Grant U01-CA184898)
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| 520 |
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|a National Institutes of Health (U.S.) (Grant R01-CA133404)
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| 520 |
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|a National Institutes of Health (U.S.) (Grant PO1-CA042063)
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| 520 |
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|a National Institutes of Health (U.S.) (Grant RO1-GM34277)
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| 520 |
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|a National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051)
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| 520 |
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|a Leukemia & Lymphoma Society of America (Grant 5198-09)
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|a en_US
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| 655 |
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|a Article
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| 773 |
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|t Cell Reports
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