The regional integration of retroviral sequences into the mosaic genomes of mammals

We have reviewed here three sets of data concerning the integration of retroviral sequences in the mammalian genome: (i) our experimental localization of a number of proviruses integrated in isochores characterized by different GC levels; (ii) results from other laboratories on the localization of retroviral sequences in open chromatin regions and/or next to CpG islands; and (iii) our compositional analysis of genes located in the neighborhood of integrated retroviral sequences. The three sets of data have provided a very consistent picture in that a compartmentalized, isopycnic integration of expressed proviruses appears to be the rule ('isopycnic' refers to the compositional match between viral and host sequences around the integration site). The results reviewed here suggest that: (i) integration of proviral sequences is targeted initially towards 'open chromatin regions'; while these exist in both GC-rich and GC-poor isochores, the 'open chromatin regions' of GC-rich isochores are the main targets for integration of retroviral sequences because of their much greater abundance; (ii) isopycnicity is associated with stability of integration; indeed, even non-expressed integrated retroviral sequences tend to show an isopycnic localization in the genome; (iii) transcription of integrated viral sequences (like transcription of host genes) appears to be associated, as a rule, with an isopycnic localization, as indicated by transcribed sequences that show an isopycnic integration and act in trans; (iv) selection plays a role in the choice of specific sites within an isopycnic region; in exceptional cases [such as mouse mammary tumor virus (MMTV) activating GC-rich oncogenes], selection may override isopycnicity. (C) 1998 Elsevier Science B.V. All rights reserved.