Chromatin domains and boundary elements

Abstract

Abstract The temporal and spatial expression of eukaryotic genes is regulated by transcription factors through their interaction with enhancer elements. After this initial interaction, enhancer-bound transcription factors cause changes in the transcription complex assembled on the promoter to activate transcription (Thompson and McKnight 1992). The mechanisms of this activation are not well understood and several alternative mechanisms have been put forward to explain this process. Transcriptional activation might involve direct protein-protein interactions through the looping of intervening sequences that separate enhancers and promoters, tracking of the transcription factors from the enhancers to the promoter, changes in chromatin structure that take place upon factor binding to its target sequence and can be transmitted to the promoter to activate transcription, or localization to a particular nuclear compartment that is permissive for gene expression. Independent of the particular details of the process, the intrinsic nature of enhancer-promoter interactions lacks the necessary specificity required for the precise temporal and spatial patterns of gene expression that underlies the development of eukaryotic organisms. To account for the observed specificity in enhancer-promoter interactions it has been proposed that the eukaryotic genome has organizational properties that rely on the ability of chromatin to establish autonomous functional units delimiting levels and patterns of gene expression. Functional specificity of transcriptional enhancers might then be imposed by the existence of chromosomal domains, discrete and topologically independent units of gene expression in which transcription from a specific promoter results only from activation by enhancers located within the same domain, whereas enhancers in a second domain are unable to act on a promoter located in the first one.