Ito T, Yamauchi M, Nishina M, Yamamichi N, Mizutani T, Ui M, Murakami M, Iba H
Department of Gene Regulation, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Biol Chem. 2001 Jan 26;276(4):2852-7. doi: 10.1074/jbc.M009633200. Epub 2000 Oct 26.
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.
Fos家族蛋白与Jun家族蛋白形成稳定的异二聚体，并且每个异二聚体通过AP-1结合位点显示出用于调节细胞生长、分化和发育的独特反式激活潜能。然而，二聚体特异性的分子机制以及促进反式激活的分子仍不明确。在此，我们表明BAF60a，一种SWI.SNF染色质重塑复合物的亚基，是Fos/Jun二聚体反式激活潜能的决定因素。BAF60a分别使用针对c-Fos和c-Jun的两个不同界面结合到Fos/Jun异二聚体的一个特定亚组。仅当存在功能性SWI.SNF复合物时，c-Fos/c-Jun（对BAF60a具有高亲和力）而非Fra-2/JunD（对BAF60a无亲和力）才能诱导内源性AP-1调控基因如胶原酶和c-met。这些结果表明Fos/Jun二聚体的一个特定亚组通过BAF60a募集SWI.SNF复合物以启动转录。
