DNA Sequence-Specific Location of Covalent DNA-Polypeptide Complexes in Eukaryotic Genomes

Abstract

Work on specific gene expression has not yet identified the factors determining the portions of genomes that are selectively expressed in different cell types. A number of genes are known that are regulated by transient interactions of cell-type-specific polypeptides with regulatory DNA sequences. However, this cell-specific regulation cannot be regarded as the basic mechanism determining the phenotype-specific patterns of gene expression because the regulatory polypeptides involved are, on their own, products of cell-type-specifically regulated genes. Alternatively, it has been suspected that the expression of specific sets of genes in various cell types could be induced by fixed interactions between nonhistone nuclear olypeptides and regulatory DNA sequences. Theoretically, a highly ordered pattern of permanent and site-specific DNA-polypeptide complexes with regulatory functions could encode the portion of the genome that is selectively expressed in each cell type. Slight variations in the locations of such complexes in variant cell types could induce the expression of different sets of genes. This hypothesis is far from being experimentally proved, however, covalent DNA-polypeptide complexes found in all eukaryotic genomes investigated show characteristics that have to be expected from such hypothetical regulatory elements: eg, they are site-specifically located in eukaryotic genomes (Neuer-Nitsche and Werner, 1987; Neuer-Nitsche et al., 1988; Werner and Neuer-Nitsche, 1989), they are associated with the nuclear matrix (Werner and Rest, 1987) and they are metabolically stable (Tsanev et al., 1989).