How signaling pathways interact with gene transcription.

Activation of inflammatory cells by extracellular stimuli such as cytokines, viruses, allergens or oxidants lead to stimulation of intracellular amplifying signalling pathways. These activation pathways lead to enhanced inflammatory gene expression through activation of transcription factors such as nuclear factor kappa B (NF-kappa B). Upon activation, NF-kappa B translocates to the nucleus where it binds specific sites in the promoter regions of responsive genes in a time-dependent manner. This leads to the alterations in the structure of the surrounding DNA/chromatin complex resulting in local unwinding of DNA. Changes in chromatin structure occur as a result of recruitment of large, essentially pre-formed, complexes that contain chromatin remodelling factors and histone acetyltransferases (HATs) such as CREB binding protein (CBP). Acetylations of histones are regulated by HATs whose activity is controlled by a number of factors including phosphorylation. Phosphorylation of HATs by signalling pathways, differentiate themselves from those controlling specific transcription factor activation and result in enhanced transcriptional activity as a result of cross-talk between signalling pathways at the level of chromatin modifications.