Exploring the interaction between the SWI/SNF chromatin remodeling complex and the zinc finger factor CTCF

The transcription factor CCCTC-binding factor (CTCF) modulates pleiotropic functions mostly related to gene expression regulation. The role of CTCF in large scale genome organization is also well established. A unifying model to explain relationships between many CTCF-mediated activities involve direct or indirect interactions with numerous protein cofactors recruited to specific binding sites. The co-association of CTCF with other architectural proteins such as cohesin, chromodomain helicases and BRG1 further support the interplay between master regulators of mammalian genome folding. Here we report a comprehensive LC-MS/MS mapping of the components of the SWI/SNF chromatin remodeling complex co-associated with CTCF including subunits belonging to the core, signature and ATPase modules. We further show that the localization patterns of representative SWI/SNF members significantly overlap with CTCF sites on transcriptionally active chromatin regions. Moreover, we provide evidence of a direct binding of the BRK-BRG1 domain to the zinc finger motifs 4-8 of CTCF, thus suggesting that these domains mediate the interaction of CTCF with the SWI/SNF complex. These findings provide an updated view of the cooperative nature between CTCF and the SWI/SNF ATP-dependent chromatin-remodeling complexes, an important step for understanding how these architectural proteins collaborate to shape the genome.