How the PIC finds favored sites on target DNA has not been fully clarified. Active genes are favored for integration, and favored sequences at the site of integration also influence the reaction. Studies of cells depeleted in PSIP1/LEDGF/p75 suggest that this protein acts as a tethering factor binding HIV PICs near integration target DNA. Access of PICs to sites on chromosomes may be significant, since centromeric alphoid repeats are disfavored for integration, perhaps due to wrapping in compact centromeric heterochromatin. Nucleosomes bound to the integration template also affect target site selection and integration complex binding.