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An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules
- Source :
- BMC Systems Biology, BMC Systems Biology, Vol 3, Iss 1, p 73 (2009)
- Publication Year :
- 2009
- Publisher :
- BioMed Central, 2009.
-
Abstract
- Background The TGF-β/SMAD pathway is part of a broader signaling network in which crosstalk between pathways occurs. While the molecular mechanisms of TGF-β/SMAD signaling pathway have been studied in detail, the global networks downstream of SMAD remain largely unknown. The regulatory effect of SMAD complex likely depends on transcriptional modules, in which the SMAD binding elements and partner transcription factor binding sites (SMAD modules) are present in specific context. Results To address this question and develop a computational model for SMAD modules, we simultaneously performed chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and mRNA expression profiling to identify TGF-β/SMAD regulated and synchronously coexpressed gene sets in ovarian surface epithelium. Intersecting the ChIP-chip and gene expression data yielded 150 direct targets, of which 141 were grouped into 3 co-expressed gene sets (sustained up-regulated, transient up-regulated and down-regulated), based on their temporal changes in expression after TGF-β activation. We developed a data-mining method driven by the Random Forest algorithm to model SMAD transcriptional modules in the target sequences. The predicted SMAD modules contain SMAD binding element and up to 2 of 7 other transcription factor binding sites (E2F, P53, LEF1, ELK1, COUPTF, PAX4 and DR1). Conclusion Together, the computational results further the understanding of the interactions between SMAD and other transcription factors at specific target promoters, and provide the basis for more targeted experimental verification of the co-regulatory modules.
- Subjects :
- Smad Proteins
SMAD
Models, Biological
Cell Line
Mothers against decapentaplegic homolog 2
03 medical and health sciences
Mice
0302 clinical medicine
Structural Biology
Transforming Growth Factor beta
Modelling and Simulation
SMAD binding
Animals
Humans
Immunoprecipitation
RNA, Messenger
Promoter Regions, Genetic
Molecular Biology
lcsh:QH301-705.5
030304 developmental biology
Oligonucleotide Array Sequence Analysis
Genetics
0303 health sciences
Genome
biology
Base Sequence
Applied Mathematics
Gene Expression Profiling
Reproducibility of Results
Transforming growth factor beta
Sequence Analysis, DNA
Chromatin
Computer Science Applications
Cell biology
Rats
Gene expression profiling
DNA binding site
Crosstalk (biology)
lcsh:Biology (General)
030220 oncology & carcinogenesis
Modeling and Simulation
biology.protein
Signal transduction
Algorithms
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 17520509
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- BMC Systems Biology
- Accession number :
- edsair.doi.dedup.....aaf27c594c850e7e528eec8df5b8f9ce