AbstractTo study the rDNA contacts with genes in three human cell lines of different origin, we used 4C approach. Our data indicate that the same set of about five hundred genes frequently shape contacts with rDNA clusters in HEK293T, K652, and hESM01 cells. Gene ontology search suggests that the genes are involved in development and morphogenesis. Approximately one hundred of these genes are highly associated with silencing by H3K27me3 mark in different normal cells, including bronchial epithelial cells, keratinocytes, myoblasts, monocytes, endothelial cells, kidney epithelial cells, and some others. We conclude that the concerted silencing of specific group of rDNA-contacting genes controlling development occurs during differentiation. We assume that the phase separation mechanisms may be involved in the rDNA-mediated silencing of a set of genes via the contacts with inactive rDNA clusters.