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Published on: February 7, 2019
Identification of SWI.SNF complex subunit BAF60a as a determinant of the transactivation potential of Fos/Jun dimers
1Department of Gene Regulation, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Abstract:
Fos family proteins form stable heterodimers with Jun family proteins, and each heterodimer shows distinctive transactivating potential for regulating cellular growth, differentiation, and development via AP-1 binding sites. However, the molecular mechanism underlying dimer specificity and the molecules that facilitate transactivation remain undefined. Here, we show that BAF60a, a subunit of the SWI.SNF chromatin remodeling complex, is a determinant of the transactivation potential of Fos/Jun dimers. BAF60a binds to a specific subset of Fos/Jun heterodimers using two different interfaces for c-Fos and c-Jun, respectively. Only when the functional SWI.SNF complex is present, can c-Fos/c-Jun (high affinity to BAF60a) but not Fra-2/JunD (no affinity to BAF60a) induce the endogenous AP-1-regulated genes such as collagenase and c-met. These results indicate that a specific subset of Fos/Jun dimers recruits SWI.SNF complex via BAF60a to initiate transcription.
Insights
BAF60a, a SWI.SNF chromatin remodeling complex subunit, determines Fos/Jun dimer transactivation potential. Specific dimers recruit SWI.SNF via BAF60a to initiate transcription of AP-1 regulated genes.
Area of Science:
- Molecular Biology
- Gene Regulation
- Chromatin Remodeling
Background:
- Fos and Jun proteins form heterodimers that regulate gene expression via AP-1 binding sites.
- The precise mechanisms governing dimer specificity and transactivation remain unclear.
Purpose of the Study:
- To identify the molecular determinants of Fos/Jun dimer specificity in transactivation.
- To elucidate the role of chromatin remodeling complexes in AP-1 mediated transcription.
Main Methods:
- Investigated the interaction between BAF60a and various Fos/Jun heterodimers.
- Assessed the ability of different heterodimers to induce AP-1 regulated genes in the presence of the SWI.SNF complex.
Main Results:
- BAF60a, a SWI.SNF subunit, acts as a specificity determinant for Fos/Jun dimer transactivation.
- BAF60a binds differentially to c-Fos/c-Jun and Fra-2/JunD heterodimers.
- Only Fos/Jun dimers with high affinity for BAF60a, in conjunction with a functional SWI.SNF complex, can induce AP-1 regulated genes like collagenase and c-met.
Conclusions:
- BAF60a is a key factor mediating the transcriptional activity of specific Fos/Jun heterodimers.
- The recruitment of the SWI.SNF complex via BAF60a is essential for initiating transcription of AP-1 target genes.
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