REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis
REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis
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DOI：
10.1016/j.cell.2005.03.013
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发表时间：
2005-05-20
期刊：
影响因子：
64.5
通讯作者：
Mandel, G
中科院分区：
文献类型：
--
作者：
Ballas, N;Grunseich, C;Mandel, G
神经元基因表达的调控对中枢神经系统发育至关重要。在这里，我们表明，REST调节从多能神经干/祖细胞和从祖细胞到成熟神经元的过渡。在向祖细胞的转变中，REST被降解到足以维持神经元基因染色质处于非活性状态的水平，但仍准备表达。随着祖细胞分化为神经元，REST及其辅阻遏物从RE 1位点解离，触发神经元基因的激活。在一些基因中，表达水平在神经元中通过CoREST/MeCP 2阻遏物复合物进一步调节，该复合物保持与不同于RE 1位点的甲基化DNA位点结合。基于这种机制的表达谱表明REST定义了成熟神经元中受可塑性影响的基因集。因此，一个多阶段的阻遏物机制控制着基因在发育过程中的有序表达，同时仍然允许对特定刺激的反应进行微调。
Regulation of neuronal gene expression is critical to central nervous system development. Here, we show that REST regulates the transitions from pluripotent to neural stem/progenitor cell and from progenitor to mature neuron. In the transition to progenitor cell, REST is degraded to levels just sufficient to maintain neuronal gene chromatin in an inactive state that is nonetheless poised for expression. As progenitors differentiate into neurons, REST and its corepressors dissociate from the RE1 site, triggering activation of neuronal genes. In some genes, the level of expression is adjusted further in neurons by CoREST/MeCP2 repressor complexes that remain bound to a site of methylated DNA distinct from the RE1 site. Expression profiling based on this mechanism indicates that REST defines a gene set subject to plasticity in mature neurons. Thus, a multistage repressor mechanism controls the orderly expression of genes during development while still permitting fine tuning in response to specific stimuli.