Chromatin complexes as aperiodic microcrystalline arrays that regulate genome organisation and expression.

Abstract

The current understanding of chromatin-mediated repression in Metazoa stems largely from work on two systems in Drosophila: heterochromatin-induced position-effect variegation and repression of the homeotic genes by the Polycomb-group of genes. A common feature of these two systems is the cooperative assembly of multimeric complexes which can epigenetically silence gene activity. Moreover, both older and more recent work has suggested that these complexes can themselves associate to give rise to larger complexes: The specificity of the association is likely to be determined by complementarity of the structural components of the complexes. Here, we aim to accommodate these, and other, features of chromatin-mediated repression in a single hypothesis, namely the crystallisation hypothesis. This hypothesis views the nucleus as being an environment that favours the formation of chromatin complexes which behave as aperiodic microcrystalline arrays constructed through the cooperative assembly of different types of lattice unit. The lattice units possess regions of structural complementarity that allow interactions between complexes. Aperiodicity confers specificity on the complexes and is a key feature of the model which, we suggest, provides a gene with a "chromosomal address." The chromosomal address allows the side-by-side alignment of homologous chromosomal regions, a properly that may be important in a variety of biologically relevant situations. Aperiodicity is also a feature of the hypothesis that is directly testable.