Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements
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-re...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/101699 https://orcid.org/0000-0003-0250-0474 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5024-9718 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6534-4774 https://orcid.org/0000-0001-8353-9316 |
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| author | 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 Gurtan, Allan M. Sharp, Phillip A. Dalin, Simona JnBaptiste, Courtney Kenneil Matthews, Bryan Yap, Yoon Sing |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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 Gurtan, Allan M. Sharp, Phillip A. Dalin, Simona JnBaptiste, Courtney Kenneil Matthews, Bryan Yap, Yoon Sing |
| author_sort | Gurtan, Allan M. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:10:38Z |
| format | Article |
| id | mit-1721.1/101699 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:10:38Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1016992022-10-02T01:11:43Z Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements 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 Gurtan, Allan M. Sharp, Phillip A. Dalin, Simona JnBaptiste, Courtney Kenneil Matthews, Bryan Yap, Yoon Sing 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 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) 2016-03-14T17:44:54Z 2016-03-14T17:44:54Z 2015-12 2015-10 Article http://purl.org/eprint/type/JournalArticle 22111247 http://hdl.handle.net/1721.1/101699 Gosline, Sara J.C., Allan M. Gurtan, Courtney K. JnBaptiste, Andrew Bosson, Pamela Milani, Simona Dalin, Bryan J. Matthews, Yoon S. Yap, Phillip A. Sharp, and Ernest Fraenkel. “Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-Transcriptional, and Histone Modification Measurements.” Cell Reports 14, no. 2 (January 2016): 310–19. https://orcid.org/0000-0003-0250-0474 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5024-9718 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6534-4774 https://orcid.org/0000-0001-8353-9316 en_US http://dx.doi.org/10.1016/j.celrep.2015.12.031 Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | 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 Gurtan, Allan M. Sharp, Phillip A. Dalin, Simona JnBaptiste, Courtney Kenneil Matthews, Bryan Yap, Yoon Sing Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title_full | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title_fullStr | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title_full_unstemmed | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title_short | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements |
| title_sort | elucidating microrna regulatory networks using transcriptional post transcriptional and histone modification measurements |
| url | http://hdl.handle.net/1721.1/101699 https://orcid.org/0000-0003-0250-0474 https://orcid.org/0000-0003-1465-1691 https://orcid.org/0000-0001-5024-9718 https://orcid.org/0000-0001-9249-8181 https://orcid.org/0000-0002-6534-4774 https://orcid.org/0000-0001-8353-9316 |
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