Classical, or constitutive (Brown, 1966), heterochromatin is a nearly ubiquitous aspect of higher eukaryotic chromosome structure and its genetic significance has been debated since its first description (Heitz, 1928, 1929). This review describes genetic studies on the heterochromatin of Drosophila and the perspectives they provide on the possible biological role(s) of constitutive heterochromatin. In addition to documenting the existence of gene loci within heterochromatin, these studies provide evidence for long-range interactions within the nucleus and involving heterochromatin. These interactions may reflect more general properties of chromatin related to the three-dimensional structure of the interphase nucleus and its effects on gene expression.

We present and review experiments that identify points of close approach of the RNA polymerase to two promoters, lac UV5 and T7 A3. We identify the contacts to the phosphates along the DNA backbone, to the N7s of guanines in the major groove and the N3s of adenines in the minor groove, and to the methyl groups of thymines. These contacts to the two promoters are strikingly homologous in space, as shown on three-dimensional models, and identify major regions of interactions lying on one side of the DNA molecule (at -35 and -16), as well as further areas extending through the Pribnow box. Both promoters are unwound similarly by the polymerase, across a region of about twelve bases extending from the middle of the Pribnow box to just beyond the RNA start site. We discuss the areas of interaction in the context of promoter homologies and promoter mutations. The disposition of the contacts in space suggests a model for the pathway along which the RNA polymerase binds to promoters.