In p16-expressing MDA-MB-435 breast-cancer cells, CTCF binds downstream of the region enriched for heterochromatin marks located within −2 kb and +1 kb of the active promoter of the p16 gene; however, in T47D breast cancer cells that contain aberrantly silenced p16, the boundary domain at −2 kb disappears and prevents CTCF binding, hereby promoting the spread of heterochromatin marks throughout the entire p16 promoter region. Here, CTCF is linked to breast cancer.