Elucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements.

TitleElucidating MicroRNA Regulatory Networks Using Transcriptional, Post-transcriptional, and Histone Modification Measurements.
Publication TypeJournal Article
Year of Publication2016
AuthorsGosline, SJC, Gurtan, AM, JnBaptiste, CK, Bosson, A, Milani, P, Dalin, S, Matthews, BJ, Yap, YS, Sharp, PA, Fraenkel, E
JournalCell Rep
Volume14
Issue2
Pagination310-9
Date Published2016 Jan 12
ISSN2211-1247
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.

DOI10.1016/j.celrep.2015.12.031
Alternate JournalCell Rep
PubMed ID26748710
PubMed Central IDPMC4831719
Grant ListP01 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