CTCF and Its Protein Partners: Divide and Rule?

CTCF is a ubiquitous transcription factor that is involved in numerous, seemingly unrelated functions. These functions include, but are not limited to, positive or negative regulation of transcription, enhancer-blocking activities at developmentally regulated gene clusters and at imprinted loci, and X-chromosome inactivation. Here, we review recent data acquired with state-of-the-art technologies that illuminate possible mechanisms behind the diversity of CTCF functions. CTCF interacts with numerous protein partners, including cohesin, nucleophosmin, PARP1, Yy1 and RNA polymerase II. We propose that CTCF interacts with one or two different partners according to the biological context, applying the Roman principle of governance, 'divide and rule' (divide et impera).