Chromosome structure and nuclear architecture: implications for gene therapy

Abstract

A reductionist view of mechanisms that control chromatin function might be appealing in its simplicity. It is tempting, for example, to view the process of gene expression as a series of simple protein-DNA and protein-protein interactions that lead, ultimately, to the assembly of an engaged transcription complex. RNA synthesis would then ensue to activate the pathway of gene expression. Yet attractive as this scheme may be, it is also clear that it bears only passing resemblance to events that occur in mammalian cells where a variety of epigenetic features might profoundly affect chromatin function. This review sets out to analyze our present knowledge of epigenetic features that influences chromatin function while placing particular emphasis on those features that are likely to impact on our ability to perform stable gene expression from ectopic genes - the major requirement of gene therapy.