ATAC乙转移酶复合体协调MAP激酶以调节JNK标基因
Tamaki Suganuma1, Arcady Mushegian, Selene K Swanson
1Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Cell
|September 4, 2010
概括
ATAC基因组酸转移酶复合体作为c-Jun的辅因子,调节基因表达并抑制细胞应激反应期间的上游信号传递.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 信号转导通路,如Jun N-终端激酶 (JNK),激活像c-Jun这样的转录因子,以调节对细胞外刺激的基因表达.
- 基因组酸转移酶 (HAT) 复合体在调节染色质结构和影响基因转录方面发挥着至关重要的作用.
研究的目的:
- 为了研究ATAC (Ada 两个含有A的) 基因素乙转移酶复合体作为c-Jun的转录辅因子的作用.
- 阐明ATAC在调节JNK点基因中的功能及其在细胞应激反应中的参与.
主要方法:
- 染色体免疫沉试验用于评估目标基因的c-Jun占用率和H4K16乙化.
- 免疫光显微镜观察在透应激下ATAC和c-Jun的同位化.
- 生物化学试验分析激酶的招募和JNK激活的抑制.
主要成果:
- ATAC复合体对于c-Jun与Jra和基因的结合以及H4K16乙化至关重要.
- 在透应激期间,ATAC与c-Jun同位,招募上游激酶 (Misshapen,MKK4,JNK) 并抑制进一步的JNK激活.
- ATAC的CG10238亚单元对于MAPK重新定位和JNK通路抑制至关重要.
结论:
- ATAC复合体在特定的目标基因中充当c-Jun的转录协活性剂.
- ATAC作为上游MAP激酶信号的负调节者,在压力时抑制JNK激活.
- ATAC集成了转录调节和信号传导调节,以响应细胞线索.
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