Yamamichi-Nishina Mitsue, Ito Taiji, Mizutani Taketoshi, Yamamichi Nobutake, Watanabe Hirotaka, Iba Hideo
Division of Host-Parasite Interaction, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
J Biol Chem. 2003 Feb 28;278(9):7422-30. doi: 10.1074/jbc.M208458200. Epub 2002 Dec 17.
The human adrenal carcinoma cell line, SW13, has been reported to be deficient in both BRG1 and Brm expression and therefore is considered to lack a functional SWI/SNF complex. We found that the original cell line of SW13 is composed of two subtypes, one that expresses neither BRG1 nor Brm (SW13(vim-)) and the another, which does express both (SW13(vim+)). The presence of BRG1 and Brm in SW13 correlates completely with the cellular ability to express such genes as vimentin, collagenase, c-met, and CD44 that were under the control of a transcription factor, AP-1, which was shown previously to require a functional SWI/SNF complex for its transactivating activity. Transient treatment with inhibitors of histone deacetylase induced a stable transition of SW13(vim-) to a cell type indistinguishable from SW13(vim+), suggesting that these two subtypes are epigenetically different. Run-on analysis indicated that, unlike these four genes driven by AP-1, transcription of the BRG1 and Brm genes in SW13(vim-) are initiated at a frequency comparable with SW13(vim+). In both SW13(vim-) and SW13(vim+) cells, the BRG1 and Brm genes were transcribed through the entire gene at a similar efficiency, indicating that their expression was completely suppressed at the post-transcriptional level in SW13(vim-) cells. We would like to propose that SW13 can spontaneously transition between two subtypes by switching expression of BRG1 and Brm at the post-transcriptional level.
据报道,人肾上腺癌细胞系SW13中BRG1和Brm的表达均缺失,因此被认为缺乏功能性的SWI/SNF复合物。我们发现,SW13的原始细胞系由两种亚型组成,一种既不表达BRG1也不表达Brm(SW13(vim-)),另一种则同时表达这两种蛋白(SW13(vim+))。SW13中BRG1和Brm的存在与细胞表达波形蛋白、胶原酶、c-met和CD44等基因的能力完全相关,这些基因受转录因子AP-1的调控,先前已证明AP-1的反式激活活性需要功能性的SWI/SNF复合物。用组蛋白脱乙酰酶抑制剂进行短暂处理可诱导SW13(vim-)稳定转变为与SW13(vim+)无法区分的细胞类型,这表明这两种亚型在表观遗传上存在差异。连续分析表明,与这四个由AP-1驱动的基因不同,SW13(vim-)中BRG1和Brm基因的转录起始频率与SW13(vim+)相当。在SW13(vim-)和SW13(vim+)细胞中,BRG1和Brm基因在整个基因上的转录效率相似,这表明它们的表达在SW13(vim-)细胞的转录后水平上被完全抑制。我们提出,SW13可以通过在转录后水平上切换BRG1和Brm的表达在两种亚型之间自发转变。