An integrated approach to characterize transcription factor and microRNA regulatory networks involved in Schwann cell response to peripheral nerve injury
Year: 2013
Type: article
Abstract: BACKGROUND: The regenerative response of Schwann cells after peripheral nerve injury is a critical process directly related to the pathophysiology of a number of neurodegenerative diseases. This SC injury response is dependent on an intricate gene regulatory program coordinated by a number of transcription factors and microRNAs, but the interactions among them remain largely unknown. Uncovering the transcriptional and post-transcriptional regulatory networks governing the Schwann cell injury response is a key step towards a better understanding of Schwann cell biology and may help develop novel therapies for related diseases. Performing such comprehensive network analysis requires systematic bioinformatics methods to integrate multiple genomic datasets. RESULTS: In this study we present a computational pipeline to infer transcription factor and microRNA regulatory networks. Our approach combined mRNA and microRNA expression profiling data, ChIP-Seq data of transcription factors, and computational transcription factor and microRNA target prediction. Using mRNA and microRNA expression data collected in a Schwann cell injury model, we constructed a regulatory network and studied regulatory pathways involved in Schwann cell response to injury. Furthermore, we analyzed network motifs and obtained insights on cooperative regulation of transcription factors and microRNAs in Schwann cell injury recovery. CONCLUSIONS: This work demonstrates a systematic method for gene regulatory network inference that may be used to gain new information on gene regulation by transcription factors and microRNAs.
Source: BMC Genomics
Institution: Washington University in St. Louis
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,090
Funders: Alvin J. Siteman Cancer Center, Hope Center for Neurological Disorders, Georgia Clinical and Translational Science Alliance, National Institutes of Health, National Institute on Aging, National Cancer Institute, National Institute of Neurological Disorders and Stroke, U.S. National Library of Medicine, National Center for Research Resources
Awards: G1114310655, G12431752, G2025301497, Novel Bioinformatics Tools for Gene Regulatory Network Inference, G299873027, Regulation of Myelination by Egr2/Nab Protein Complexes, Washington University Center for Translational Neuroscience, Washington University Institute of Clinical and Translational Sciences (UL1), G8242737674, G8405709672, G9000007441, G9000063882, G9000319192, Compromised LDH activity causes motor deficits and hastens ALS progression, Cancer Center Support Grant, G953005567
OpenAlex ID: W1971790889