Chicken domains of alpha- and beta-globin genes constitute traditional models to study possible relationships between the structural and functional organization of the eukaryotic genome. Recent evidence indicates that these two genomic domains differ significantly in genomic organization as well as in their mode of packaging into chromatin. In this review, we present a comparative analysis of the chicken alpha- and beta-globin gene clusters. The data are discussed in terms of the "domain hypothesis of the eukaryotic genome organization." On the basis of the results of our analysis, we present arguments for the existence of three distinct mechanisms that corroborate in the activation/repression of genomic domains. These mechanisms are (1) the relocation of genomic domains into nuclear compartments, (2) the long-term modifications of the mode of chromatin packaging within domains, and (3) the domain activation by continuous action of multiple transcription factors and remodeling complexes.