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An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules
Huaxia Qin1, Michael W Y Chan, Sandya Liyanarachchi
1Human Cancer Genetics Program, Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210, USA. huaxia.qin@gmail.com
BMC Systems Biology
|July 21, 2009
Summary
Researchers modeled SMAD transcriptional modules to understand TGF-beta/SMAD pathway regulation. This reveals interactions between SMAD and other transcription factors at target promoters, aiding experimental verification.
Area of Science:
- Molecular biology
- Systems biology
- Bioinformatics
Background:
- The TGF-beta/SMAD pathway is a key signaling network with complex crosstalk.
- Global networks downstream of SMAD are largely unknown.
- SMAD complex regulation likely involves specific transcriptional modules.
Purpose of the Study:
- To develop a computational model for SMAD modules.
- To identify TGF-beta/SMAD regulated gene sets.
- To understand SMAD interactions with other transcription factors.
Main Methods:
- Chromatin immunoprecipitation followed by microarray analysis (ChIP-chip).
- mRNA expression profiling.
- Random Forest algorithm for data mining.
Main Results:
- Identified 150 direct TGF-beta/SMAD targets in ovarian surface epithelium.
- Grouped 141 targets into 3 co-expressed gene sets.
- Modeled SMAD modules including SMAD binding elements and up to 2 partner transcription factor binding sites.
Conclusions:
- Computational results advance understanding of SMAD and transcription factor interactions.
- Provides a basis for experimental verification of co-regulatory modules.
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