The meaning of gene positioning

Abstract

There is no doubt that genomes are organized nonrandomly in the nucleus of higher eukaryotes. But what is the functional relevance of this nonrandomness? In this Essay, we explore the biological meaning of spatial gene positioning by examining the functional link between the activity of a gene and its radial position in the nucleus.

Figure 1. Radial Positioning of Genes

(A) Active genes can be anywhere in the nucleus. The radial positions of biallelically expressed genes often vary between the two homologous alleles in the same nucleus. Shown are the locations of the two alleles of the IGH (green) and MYC (red) genes in human lymphocytes. (B) Functional significance of radial positioning. (Top) Active genes (green) exhibit a large range of radial positions; the precise radial position of a locus does not correlate with its activity level. (Middle) Inactive genes (red) may associate with heterochromatin blocks at various radial positions. (Bottom) In contrast to radial positioning, physical association with the nuclear periphery is often linked to silencing. Genes that are in close proximity to the nuclear envelope but do not physically interact with it may be active.