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How signaling pathways interact with gene transcription.
M Kagoshima1, B Cosio, I M Adcock
1Thoracic Medicine, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY.
Summary
Inflammatory cell activation triggers signaling pathways that enhance gene expression via nuclear factor kappa B (NF-kappa B). This process involves chromatin remodeling and histone acetylation, crucial for inflammatory responses.
Area of Science:
- Molecular Biology
- Cellular Biology
- Immunology
Background:
- Extracellular stimuli like cytokines and viruses activate inflammatory cells.
- This activation stimulates intracellular signaling pathways, leading to enhanced inflammatory gene expression.
- Nuclear factor kappa B (NF-kappa B) is a key transcription factor in these pathways.
Purpose of the Study:
- To elucidate the molecular mechanisms linking inflammatory cell activation to gene expression.
- To investigate the role of transcription factors and chromatin modifications in inflammatory responses.
Main Methods:
- Analysis of intracellular signaling pathways.
- Study of NF-kappa B translocation and DNA binding.
- Investigation of chromatin remodeling and histone acetyltransferase (HAT) activity.
Main Results:
- NF-kappa B activation leads to its nuclear translocation and binding to specific gene promoter regions.
- Chromatin remodeling complexes, including HATs like CREB binding protein (CBP), are recruited.
- Phosphorylation of HATs by signaling pathways enhances transcriptional activity through cross-talk.
Conclusions:
- Inflammatory cell activation involves a cascade of signaling events culminating in NF-kappa B-mediated gene expression.
- Chromatin modifications, particularly histone acetylation regulated by HATs, play a critical role in amplifying inflammatory gene transcription.
- Cross-talk between signaling pathways at the chromatin level is essential for regulating inflammatory gene expression.