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首页> 外文期刊>Neuron >Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain
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Promoter decommissioning by the NuRD chromatin remodeling complex triggers synaptic connectivity in the mammalian brain

机译：NuRD染色质重塑复合体启动子退役触发哺乳动物脑中的突触连接

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Precise control of gene expression plays fundamental roles in brain development, but the roles of chromatin regulators in neuronal connectivity have remained poorly understood. We report that depletion of the NuRD complex by invivo RNAi and conditional knockout of the core NuRD subunit Chd4 profoundly impairs the establishment of granule neuron parallel fiber/Purkinje cell synapses in the rodent cerebellar cortex invivo. By interfacing genome-wide sequencing of transcripts and ChIP-seq analyses, we uncover a network of repressed genes and distinct histone modifications at target gene promoters that are developmentally regulated by the NuRD complex in the cerebellum invivo. Finally, in a targeted invivo RNAi screen of NuRD target genes, we identify a program of NuRD-repressed genes that operate as critical regulators of presynaptic differentiation in the cerebellar cortex. Our findings define NuRD-dependent promoter decommissioning as a developmentally regulated programming mechanism that drives synaptic connectivity in the mammalian brain.
机译：基因表达的精确控制在大脑发育中起着基本作用，但是染色质调节剂在神经元连通性中的作用仍然知之甚少。我们报告说，体内RNAi对NuRD复合物的消耗和核心NuRD亚基Chd4的条件敲除严重损害了啮齿类小脑皮层体内的颗粒神经元平行纤维/ Purkinje细胞突触的建立。通过接口全基因组转录本和ChIP-seq分析的测序，我们发现了受压基因网络和目标基因启动子上不同的组蛋白修饰，这些基因受小脑体内NuRD复合物的发育调控。最后，在针对NuRD目标基因的有针对性的RNAi体内筛选中，我们确定了NuRD抑制基因的程序，该程序可作为小脑皮层中突触前分化的关键调控因子。我们的发现将依赖NuRD的启动子退役定义为驱动哺乳动物脑中突触连接的发育受调控的编程机制。

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