Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2
Repression of PML nuclear body-associated transcription by oxidative stress-activated Bach2
复制标题
DOI：
10.1128/mcb.24.8.3473-3484.2004
复制
发表时间：
2004-04-01
影响因子：
5.3
通讯作者：
Igarashi, K
中科院分区：
文献类型：
--
作者：
Tashiro, S;Muto, A;Igarashi, K
一些证据表明，基因表达不仅受转录因子和DNA之间的相互作用调节，还受细胞核高阶结构的调节。PML小体是最重要的核亚结构之一，在细胞凋亡和应激反应过程中参与转录调控。Bach2是btb -碱性区亮氨酸拉链因子家族的成员，可抑制由12- o - tetradecanoylphorol -13-acetate响应元件、Maf识别元件和抗氧化响应元件指导的转录活性。在氧化应激下，Bach2形成与PML小体相关的核灶。在这里，我们证明了与PML小体相关的转录活性被PML小体周围Bach2的募集选择性地抑制。光漂白实验后的荧光恢复显示Bach2在核灶中快速转换。包括BTB结构域在内的Bach2 n端区域对焦点的形成至关重要。Bach2的sumo化是PML小体周围蛋白募集所必需的。这些观察结果代表了在氧化应激下由序列特异性转录因子调节与PML体相关的转录活性的第一个例子。
Several lines of evidence suggest that gene expression is regulated not only by the interaction between transcription factors and DNA but also by the higher-order architecture of the cell nucleus. PML bodies are one of the most prominent nuclear substructures which have been implicated in transcription regulation during apoptosis and stress responses. Bach2 is a member of the BTB-basic region leucine zipper factor family and represses transcription activity directed by the 12-O-tetradecanoylphorbol-13-acetate response element, the Maf recognition element, and the antioxidant-responsive element. Bach2 forms nuclear foci associated with PML bodies upon oxidative stress. Here, we demonstrate that transcription activity associated with PML bodies is selectively repressed by the recruitment of Bach2 around PML bodies. Fluorescence recovery after photobleaching experiments revealed that Bach2 showed rapid turnover in the nuclear foci. The Bach2 N-terminal region including the BTB domain is essential for the focus formation. Sumoylation of Bach2 is required for the recruitment of the protein around PML bodies. These observations represent the first example of modulation of transcription activity associated with PML bodies by a sequence-specific transcription factor upon oxidative stress.