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Transcriptional network dynamics in macrophage activation
Roland Nilsson1, Vladimir B Bajic, Harukazu Suzuki
1Center for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden.
Genomics
|May 16, 2006
Summary
This study reveals dynamic transcriptional networks in mouse macrophages responding to bacterial lipopolysaccharide (LPS). The findings define regulatory modules and suggest new roles for transcription factors ATF-3 and NRF-2 in inflammation.
Area of Science:
- Genomics
- Systems Biology
- Immunology
Background:
- Transcriptional regulatory networks control cell functions but are difficult to study in mammals.
- Understanding these networks is crucial for cell differentiation and response to stimuli.
Purpose of the Study:
- To perform a genome-wide network analysis of transcriptional regulation in mouse macrophages stimulated with bacterial lipopolysaccharide (LPS).
- To uncover dynamic regulatory modules involved in the inflammatory response.
Main Methods:
- Combined time-series cap analysis of gene expression with in silico prediction of transcription factor binding sites.
- Integrated microarray and qPCR time-series expression data with promoter analysis.
Main Results:
- Identified dynamic subnetworks in the macrophage LPS response.
- Characterized regulatory modules specific to the inflammatory response.
- Suggested novel roles for transcription factors ATF-3 and NRF-2.
Conclusions:
- The developed system approach is applicable to understanding cellular differentiation in higher eukaryotes.
- This study provides insights into the complex transcriptional regulation during inflammation.