What controls the behavior of the chromatin associated with the provirus?
The link between chromatin remodeling and proviral activity seems incontrovertible, but how is it controlled? One possible factor is the site of integration. A study of 35 HIV-1-infected clones found heterogeneity in their individual levels of gene expression. There was no correlation between the expression level of the integrated provirus and a second transfected construct in the same clone, again implicating the local environment in controlling proviral expression [37]. Analyzing the accessibility of restriction enzymes to DNA as a guide to nucleosome remodeling showed that this did correlate with the level of gene expression, despite a lack of correlation between gene expression and promoter methylation [37]. In addition, latent HIV-1 proviruses are frequently found integrated near alphoid repeats, which are frequently found in heterochromatin [38,39]. This association with heterochromatin was further supported by a large-scale study of 971 HIV-1 integration sites that revealed that
