Exploring the Interaction between the SWI/SNF Chromatin Remodeling Complex and the Zinc Finger Factor CTCF

探索 SWI/SNF 染色质重塑复合物与锌指因子 CTCF 之间的相互作用

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作者:Mariangela Valletta, Rosita Russo, Ilaria Baglivo, Veronica Russo, Sara Ragucci, Annamaria Sandomenico, Emanuela Iaccarino, Menotti Ruvo, Italia De Feis, Claudia Angelini, Sara Iachettini, Annamaria Biroccio, Paolo Vincenzo Pedone, Angela Chambery

Abstract

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 among many CTCF-mediated activities involves 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 supports the interplay between master regulators of mammalian genome folding. Here, we report a comprehensive LC-MS/MS mapping of the components of the switch/sucrose nonfermentable (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.

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