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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Gosline SJ,Gurtan AM,JnBaptiste CK,Bosson A,Milani P,Dalin S,Matthews BJ,Yap YS,Sharp PA,Fraenkel Edoi
10.1016/j.celrep.2015.12.031subject
Has Abstractpub_date
2016-01-12 00:00:00pages
310-9issue
2issn
2211-1247pii
S2211-1247(15)01455-2journal_volume
14pub_type
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