Activating the PARP-1 sensor component of the Groucho/TLE1 corepressor complex mediates a CaMKinase IIδ-dependent neurogenic gene activation pathway
Activating the PARP-1 sensor component of the Groucho/TLE1 corepressor complex mediates a CaMKinase IIδ-dependent neurogenic gene activation pathway
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DOI：
10.1016/j.cell.2004.11.017
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发表时间：
2004-12-17
期刊：
影响因子：
64.5
通讯作者：
Rosenfeld, MG
中科院分区：
文献类型：
--
作者：
Ju, BG;Solum, D;Rosenfeld, MG
响应精确的时间/空间信号而切换基因抑制和激活的特定模式对于正常发育至关重要。在这里，我们报告了一个途径，其中CaMKII delta的诱导触发了一个意想不到的开关的HES 1转录因子的功能，从一个TLE依赖性阻遏物激活神经元分化所需的。这些事件是基于groucho/TLE-辅阻遏物复合物的多聚腺苷三磷酸核糖聚合酶1（PARP-1）传感器组分的激活，介导辅阻遏物复合物从HES 1调节的启动子中被消除。同时，CaMKII delta介导所需的HES 1磷酸化，以允许神经源性基因激活，揭示了一个特定的信号通路的能力，以调节去阻遏和随后的辅激活因子招募事件所需的转录激活的神经源性程序。PARP-1作为激活特定神经基因程序所需的受调节的启动子特异性交换因子的鉴定可能是类似分子机制的原型。
Switching specific patterns of gene repression and activation in response to precise temporal/spatial signals is critical for normal development. Here we report a pathway in which induction of CaMKIIdelta triggers an unexpected switch in the function of the HES1 transcription factor from a TLE-dependent repressor to an activator required for neuronal differentiation. These events are based on activation of the poly(ADPribose) polymerase1 (PARP-1) sensor component of the groucho/TLE-corepressor complex mediating dismissal of the corepressor complex from HES1-regulated promoters. In parallel, CaMKIIdelta mediates a required phosphorylation of HES1 to permit neurogenic gene activation, revealing the ability of a specific signaling pathway to modulate both the derepression and the subsequent coactivator recruitment events required for transcriptional activation of a neurogenic program. The identification of PARP-1 as a regulated promoter-specific exchange factor required for activation of specific neurogenic gene programs is likely to be prototypic of similar molecular mechanisms.