Selection of favorable integration sites is required for efficient HIV infection. Integration shows no sequence- specificity, and although some factors that support efficient integration have been identified, cells depleted for them are still infected. Some studies have suggested that nucleosomes could play a role as a substrate for integration. Here, Wang et al. (2007) used pyrosequencing to generate more than ~40,000 unique integration sites, and with a nucleosome positioning prediction tool (discussed previously here), they identified a pattern for integration: It was "favored at phosphate backbone sites at the edges of outwardly facing major grooves" of chromatin. ENCODE annotations correlated positively the generated integration sites with active expression epigenetic marks (H3 acetylation, H4 acetylation, H3K4 methylation), and negatively with silencing modifications (H3K27 trimethylation and CpG methylation). Authors suggested that the viral integrase could interact with methylated histone tails, or with other chromatin associated proteins, or simply these epigenetic modifications could be only markers of favored integration sites, with no active role. Besides, this novel experimental design could be useful to evaluate the integration sites not only for other viruses, but also for the toxicity problems sometimes associated with gene therapy viral vectors.
Wang, GP. et al. 2007 Jun 1; Genome Res 17:1186-1194
epigenetics
