Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons
Yin Yang 1 Is a Critical Repressor of Matrix Metalloproteinase-9 Expression in Brain Neurons
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DOI：
10.1074/jbc.m804540200
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发表时间：
2008-12-12
影响因子：
4.8
通讯作者：
Kaczmarek, Leszek
中科院分区：
文献类型：
--
作者：
Rylski, Marcin;Amborska, Renata;Kaczmarek, Leszek
膜去极化控制大脑生理学和病理学中持久的适应性神经元变化。这种反应被认为是基因表达依赖性的。然而值得注意的是，仅描述了几种在非去极化神经元中活跃的基因抑制因子。在本研究中，我们发现在体内未刺激的大鼠海马体以及原代培养的非去极化脑神经元中，转录调节因子 Yin Yang 1 (YY1) 与近端 Mmp-9 启动子结合并强烈抑制 Mmp-9 转录。此外，我们证明单泛素化和 CtBP1（C 端结合蛋白 1）结合的 YY1 调节大鼠脑神经元中 Mmp-9 mRNA 的合成，显然通过 HDAC3 依赖性组蛋白脱乙酰化控制其转录。总之，我们的数据表明 YY1 通过表观遗传机制发挥对 MMP-9 神经元表达的控制。由于 MMP-9 最近被证明在生理和病理神经元可塑性中发挥着关键作用，因此 YY1 也可能与这些现象有关。
Membrane depolarization controls long lasting adaptive neuronal changes in brain physiology and pathology. Such responses are believed to be gene expression-dependent. Notably, however, only a couple of gene repressors active in nondepolarized neurons have been described. In this study, we show that in the unstimulated rat hippocampus in vivo, as well as in the nondepolarized brain neurons in primary culture, the transcriptional regulator Yin Yang 1 (YY1) is bound to the proximal Mmp-9 promoter and strongly represses Mmp-9 transcription. Furthermore, we demonstrate that monoubiquitinated and CtBP1 (C-terminal binding protein 1)-bound YY1 regulates Mmp-9 mRNA synthesis in rat brain neurons controlling its transcription apparently via HDAC3-dependent histone deacetylation. In conclusion, our data suggest that YY1 exerts, via epigenetic mechanisms, a control over neuronal expression of MMP-9. Because MMP-9 has recently been shown to play a pivotal role in physiological and pathological neuronal plasticity, YY1 may be implicated in these phenomena as well.