Interactome mapping defines BRG1, a component of the SWI/SNF chromatin remodeling complex, as a new partner of the transcriptional regulator CTCF

• Published in: The Journal of biological chemistry Vol. 294; no. 3; pp. 861 - 873
• Main Authors: Marino, Maria Michela, Rega, Camilla, Russo, Rosita, Valletta, Mariangela, Gentile, Maria Teresa, Esposito, Sabrina, Baglivo, Ilaria, De Feis, Italia, Angelini, Claudia, Xiao, Tioajiang, Felsenfeld, Gary, Chambery, Angela, Pedone, Paolo Vincenzo
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 18.01.2019; American Society for Biochemistry and Molecular Biology
• Subjects: BRG1; CCCTC-Binding Factor - genetics; CCCTC-Binding Factor - metabolism; Cell Line, Tumor; chromatin; Chromatin Assembly and Disassembly; CTCF; DNA Helicases - genetics; DNA Helicases - metabolism; Genomics and Proteomics; Humans; Interactomics; mass spectrometry (MS); Multiprotein Complexes - genetics; Multiprotein Complexes - metabolism; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; protein–protein interaction; proteomics; SWI/SNF; transcription factor; Transcription Factors - genetics; Transcription Factors - metabolism; transcriptional regulation; transcription factor; proteomics; BRG1; transcriptional regulation; Interactomics; SWI/SNF; protein–protein interaction; CTCF; chromatin; mass spectrometry (MS)
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.RA118.004882

The highly conserved zinc finger CCCTC-binding factor (CTCF) regulates genomic imprinting and gene expression by acting as a transcriptional activator or repressor of promoters and insulator of enhancers. The multiple functions of CTCF are accomplished by co-association with other protein partners and are dependent on genomic context and tissue specificity. Despite the critical role of CTCF in the organization of genome structure, to date, only a subset of CTCF interaction partners have been identified. Here we present a large-scale identification of CTCF-binding partners using affinity purification and high-resolution LC-MS/MS analysis. In addition to functional enrichment of specific protein families such as the ribosomal proteins and the DEAD box helicases, we identified novel high-confidence CTCF interactors that provide a still unexplored biochemical context for CTCF's multiple functions. One of the newly validated CTCF interactors is BRG1, the major ATPase subunit of the chromatin remodeling complex SWI/SNF, establishing a relationship between two master regulators of genome organization. This work significantly expands the current knowledge of the human CTCF interactome and represents an important resource to direct future studies aimed at uncovering molecular mechanisms modulating CTCF pleiotropic functions throughout the genome.