Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements
| Autor: | Gurtan, Allan M., JnBaptiste, Courtney K., Bosson, Andrew, Milani, Pamela, Matthews, Bryan J., Yap, Yoon S., Sharp, Phillip A., Fraenkel, Ernest, Gosline, Sara Jane Calafell, Dalin, Simona, JnBaptiste, Courtney Kenneil, Matthews, Bryan, Yap, Yoon Sing |
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| Přispěvatelé: | Massachusetts Institute of Technology. Department of Biological Engineering, Massachusetts Institute of Technology. Department of Biology, Koch Institute for Integrative Cancer Research at MIT, Gosline, Sara Jane Calafell, Gurtan, Allan M., JnBaptiste, Courtney K., Bosson, Andrew, Milani, Pamela, Dalin, Simona Sara, Matthews, Bryan J., Yap, Yoon S., Sharp, Phillip A., Fraenkel, Ernest |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Genetics biology Gene regulatory network Computational biology Article General Biochemistry Genetics and Molecular Biology 3. Good health Histone Code MicroRNAs 03 medical and health sciences 030104 developmental biology lcsh:Biology (General) Transcription (biology) microRNA Gene expression biology.protein Humans Histone code Gene Regulatory Networks Epigenetics Transcription factor lcsh:QH301-705.5 Transcription Factors Dicer |
| Zdroj: | Elsevier Cell Reports, Vol 14, Iss 2, Pp 310-319 (2016) |
| Popis: | 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. National Institutes of Health (U.S.) (Grant U54-CA112967) National Institutes of Health (U.S.) (Grant R01-GM089903) National Institutes of Health (U.S.) (Grant U01-CA184898) National Institutes of Health (U.S.) (Grant R01-CA133404) National Institutes of Health (U.S.) (Grant PO1-CA042063) National Institutes of Health (U.S.) (Grant RO1-GM34277) National Cancer Institute (U.S.) (Koch Institute Support (Core) Grant P30-CA14051) Leukemia & Lymphoma Society of America (Grant 5198-09) |
| Databáze: | OpenAIRE |
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