Features of nuclear architecture that influence gene expression in higher eukaryotes: confronting the enigma of epigenetics.

Complex mechanisms that influence gene expression in mammalian cells have been studied intensively over recent years. Genetic elements that control both the tissue specific patterns and levels of gene expression together with the proteins they bind have been characterised in detail and are clearly pivotal in activating pathways of gene expression. But it is also clear that the behaviour of these genetic elements is complicated by epigenetic factors, so that their introduction into cells with the necessary developmental history-and hence appropriate global concentrations of essential transcription factors-will not guarantee the desired levels of transcription. Recent experiments have reinforced this view and confirmed that apparently critical functions performed by defined genetic elements at certain chromosomal sites are not inevitably recapitulated at other chromosomal locations. Hence, a re-evaluation of the function of critical control elements is required using experimental systems that simplify the range of factors arising from local chromatin organisation. In this way, it should be possible to reveal the intricacies of gene expression that might eventually allow us to reproduce natural levels of expression from artificial gene constructs in human cells. J. Cell. Biochem. Suppl. 35:69-77, 2000. Copyright 2001 Wiley-Liss, Inc.