Transcription factors, chromatin and cancer

Transcription factors, chromatin all chromatin-modifying, enzymes are key components ill a complex network through Which the genome interacts with its environment. For many transcription factors, binding Motifs are found adjacent to the promoter regions of a large proportion of genes, requiting mechanisms that confer binding specificity in any given cell type. These include association of the factor with other proteins and packaging of DNA, as chromatin, at the binding sequence so as to inhibit or facilitate binding. Recent evidence suggests that specific post-translational modifications of the histones packaging promoter DNA can help guide transcription factors to selected sites. The enzymes that put such Modifications in place are dependent oil metabolic components (e.g. acetyl CoA, S-adenosyl methionine) and susceptible to inhibition or activation by environmental factors. Local patterns of histone modification can be altered or maintained through direct interaction between the transcription factor and histone modifying enzymes. The functional consequences of transcription factor binding are also dependent oil protein modifying enzymes, particularly those that alter lysine methylation at selected residues. Remarkably, the role of these enzymes is not limited to promoter-proximal events, but call be linked to changes ill the intranuclear location of target genes. In this review we describe results that begin to define how transcription factors, chromatin and environmental variables interact and how these interactions are sub-treated ill cancer. We focus Oil the nuclear receptor family of transcription factors, where binding of ligands Such as steroid hormones and dietary derived factors provides all extra level of environmental input. (C) 2008 Elsevier Ltd. All rights reserved.