177, Brown et al. follow the nuclear positioning of the globin genes during erythroid differentiation and find that they are often close to each other during active transcription. However, such associations do not appear to be a requirement for transcriptional regulation, but rather a consequence of it.
The α- and β-globin genes are highly transcribed for a brief time during the maturation of red blood cells, with each gene producing about the same amount of mRNA. But the chromosomal contexts for the genes are very different. The human α-globin genes lie in a gene-dense subtelomeric region that is constitutively in an open chromatin conformation. The β-globin genes are in an AT-rich region that is open only during erythroblast development.
At the point of maximal transcription, the α-globin genes were frequently decondensed and distinct from their chromosomal territories. By contrast, the β-globin genes remained close to their native chromosome arms, as did the mouse α-globin genes, which lie in a less gene-rich region than their human counterparts.
Moreover, the human α-globin alleles associated near one another in approximately half of the transcribing cells examined, as did α- and β-globin alleles. β-globin alleles, in contrast, were almost never in close proximity to each other. Finally, the α-globin alleles were more likely to be in contact with large aggregates of splicing factors called speckles.
Thus, despite the functional similarities of human and mouse α- and β-globin genes, the loci show differing patterns of nuclear localization and interaction. Brown et al. conclude that gene positioning in the nucleus depends on multiple factors, including gene density and chromosomal location. They hypothesize that rapidly transcribed genes—or at least those that are potentially mobile—can be pulled near one another as large aggregates of transcription and processing factors accumulate in their vicinity. Already, they have seen similar associations between other coexpressed genes.