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Direct interaction between Ku70/86 and BRG1 are required for nuclear receptor‐dependent transcriptional activation in vivo
Author(s) -
Trotter Kevin W.,
Archer Trevor K
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.892.4
Subject(s) - swi/snf , chromatin remodeling , chromatin , ku70 , microbiology and biotechnology , smarca4 , chromatin immunoprecipitation , chromatin structure remodeling (rsc) complex , transcription factor , transcription coregulator , transcription (linguistics) , biology , dna binding domain , chemistry , genetics , dna repair , dna , promoter , gene , gene expression , linguistics , philosophy
The mammalian BRG1 chromatin remodeling complex has been shown to regulate gene expression by altering local chromatin structure and recruiting transcription factors to sequence‐specific DNA. BRG1, the central ATPase of the SWI/SNF complex, is critical for the functional activity of nuclear receptor complexes. Analysis using BRG1 mutants suggests the remodeling protein contains functional motifs outside of the ATPase domain that are important for transcription. To further examine these conserved domains we performed Y2H‐screens using baits spanning the BRG1 N‐terminus to identify proteins that may be required for SWI/SNF activity. Several proteins were found to associate with the N‐terminus of BRG1, including proteins involved in DNA repair, replication, transcription, and modulation of chromatin architecture. Interestingly, Ku70 was found to associate with the BRG1 region encompassing the conserved HSA and BRK domains. Ku70 functions as a single‐stranded DNA‐dependent ATP‐dependent helicase and plays a key role in multiple nuclear processes such as DNA repair and V(D)J recombination. Transcription assays and chromatin immunoprecipitation studies suggest Ku and components of the TopoIIâ/PARP1 complex may be necessary components of the SWI/SNF complex required for nuclear‐receptor mediated transcriptional activation in vivo.