Signal transducers and activators of transcription-1 (STAT1) regulates microRNA transcription in interferon γ-stimulated HeLa cells

Guohua Wang, Yadong Wang, Mingxiang Teng, Denan Zhang, Lang Li, Yunlong Liu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Constructing and modeling the gene regulatory network is one of the central themes of systems biology. With the growing understanding of the mechanism of microRNA biogenesis and its biological function, establishing a microRNA-mediated gene regulatory network is not only desirable but also achievable. Methodology: In this study, we propose a bioinformatics strategy to construct the microRNA-mediated regulatory network using genome-wide binding patterns of transcription factor(s) and RNA polymerase II (RPol II), derived using chromatin immunoprecipitation following next generation sequencing (ChIP-seq) technology. Our strategy includes three key steps, identification of transcription start sites and promoter regions of primary microRNA transcripts using RPol II binding patterns, selection of cooperating transcription factors that collaboratively function with the transcription factors targeted by ChIP-seq assay, and construction of the network that contains regulatory cascades of both transcription factors and microRNAs. Principal Findings: Using CAMDA (Critical Assessment of Massive Data Analysis) 2009 data set that includes ChIP-seq data on RPol II and STAT1 (signal transducers and activators of transcription 1) in HeLa S3 cells in control condition and with interferon γ stimulation, we first identified promoter regions of 83 microRNAs in HeLa cells. We then identified two potential STAT1 collaborating factors, AP-1 and C/EBP (CCAAT enhancer-binding proteins), and further established eight feedback network elements that may regulate cellular response during interferon γ stimulation. Conclusions: This study offers a bioinformatics strategy to provide testable hypotheses on the mechanisms of microRNA-mediated transcriptional regulation, based upon genome-wide protein-DNA interaction data derived from ChIP-seq experiments.

Original languageEnglish
Article numbere11794
JournalPLoS One
Volume5
Issue number7
DOIs
StatePublished - 2010

Fingerprint

STAT1 Transcription Factor
interferons
Transcription
MicroRNAs
microRNA
HeLa Cells
Interferons
transcription (genetics)
RNA Polymerase II
Transcription Factors
DNA-directed RNA polymerase
transcription factors
Genes
cells
Gene Regulatory Networks
Bioinformatics
Computational Biology
Genetic Promoter Regions
bioinformatics
promoter regions

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Signal transducers and activators of transcription-1 (STAT1) regulates microRNA transcription in interferon γ-stimulated HeLa cells. / Wang, Guohua; Wang, Yadong; Teng, Mingxiang; Zhang, Denan; Li, Lang; Liu, Yunlong.

In: PLoS One, Vol. 5, No. 7, e11794, 2010.

Research output: Contribution to journalArticle

Wang, Guohua ; Wang, Yadong ; Teng, Mingxiang ; Zhang, Denan ; Li, Lang ; Liu, Yunlong. / Signal transducers and activators of transcription-1 (STAT1) regulates microRNA transcription in interferon γ-stimulated HeLa cells. In: PLoS One. 2010 ; Vol. 5, No. 7.
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