Functional gene expression domains: defining the functional unit of eukaryotic gene regulation

The term functional domain is often used to describe the region containing the cis acting sequences that regulate a gene locus. "Strong" domain models propose that the domain is a spatially isolated entity consisting of a reg ion of extended accessible chromatin bordered by insulators that have evolv ed to act as functional boundaries, However, the observation that independe ntly regulated loci can overlap partially or completely raises questions ab out functional requirements for physically isolated domain structures, An a lternative model, the "weak" domain model, proposes that domain structure i s determined by the distribution of binding sites for positively acting fac tors, without a requirement for functional boundaries. The domain would eff ectively be the region that contains these factor-binding sites, Specificit y of promoter-enhancer interactions would play a major role in maintaining the functional autonomy of adjacent genes, Sequences that interfere with th ese interactions (frequently characterised as insulators) would be selected against if they occurred within the domain but not at the edges, or in the interdomain regions. As a result, insulators would often be found near the borders of domains without necessarily being selected to act as boundaries . (C) 2000 John Wiley & Sons, Inc.