ИСТИНА

Vertebrate domains of alpha- and beta-globin genes constitute popular models for studying mechanisms that control expression of tissue specific genes. Interestingly, in warm-blooded vertebrates alpha- and beta-globin genes are segregated in clusters located at different chromosomes and organized in chromatin domains of different type. Alpha-globin genes reside in permanently open (DNase-sensitive) chromatin domain while beta-globin genes demonstrate cell lineage-specific switch of DNase I sensitivity. To get more insight into organization and evolution of alpha-globin gene clusters, we have compared organization and spatial structure of chicken alpha-globin gene cluster and joint cluster of α/β-globin genes of Danio rerio. We have found that the major α/β-globin gene locus of Danio rerio is spatially and structurally segregated into two stage-specific sub-loci separated by CTCF-dependent insulator. Of these two only the sub-locus harboring adult α- and β-globin genes is controlled by the evolutionary conserved enhancer element that is similar to MRE of avian and mammalian α-globin gene loci. Spatial interactions of the enhancer with the promoters of adult globin genes organize this sub-locus into a compact globular domain. The sub-locus harboring embryo-larval α- and β-globin genes possesses linear configuration in erythrocytes of both larva and adult fish. Taking into account the fact that avian and mammalian α-globin gene loci possess globular spatial organization in erythroid cells we propose that the globular spatial organization of globing gene domains has certain evolutionary advantages over the linear spatial organization. This may be due to a possibility of coordinate regulation of several genes by a common enhancer. For this reason linear section of the ancestral α/β-globin gene locus was lost in evolution while the globular section evolved into segregated clusters of α- and β-globin genes.