Title | Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Gosline, SJC, Gurtan, AM, JnBaptiste, CK, Bosson, A, Milani, P, Dalin, S, Matthews, BJ, Yap, YS, Sharp, PA, Fraenkel, E |
Journal | Cell Rep |
Volume | 14 |
Issue | 2 |
Pagination | 310-9 |
Date Published | 2016 Jan 12 |
ISSN | 2211-1247 |
Abstract | 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. |
DOI | 10.1016/j.celrep.2015.12.031 |
Alternate Journal | Cell Rep |
PubMed ID | 26748710 |
PubMed Central ID | PMC4831719 |
Grant List | P01 CA042063 / CA / NCI NIH HHS / United States R01 CA133404 / CA / NCI NIH HHS / United States R01 GM034277 / GM / NIGMS NIH HHS / United States R01 GM089903 / GM / NIGMS NIH HHS / United States U01 CA184898 / CA / NCI NIH HHS / United States U54 CA112967 / CA / NCI NIH HHS / United States |