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Abstract：
Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein\'s biological functions in dopamine-based neurogenesis.
摘要：
核受体相关1（Nurr1）蛋白已被确定为中脑多巴胺能神经发生的强制性转录因子，但是人类NURR1靶基因的全球集合仍未被探索。这里,我们通过分析三种人类神经干细胞(hNSC)系中NURR1和NURR1共有位点的全基因组差异表达,确定了NURR1的直接基因靶标.通过定量PCR在hNSC和小鼠胚胎大脑中验证微阵列数据，并通过与已发表的人类数据进行比较，包括全基因组关联研究命中和BioGPS基因表达图集。我们的分析确定了约40个NURR1直接靶基因，他们中的许多人参与必需的蛋白质模块，如突触形成，大脑发育过程中的神经元细胞迁移，细胞周期进程和DNA复制。具体来说,突触形成和神经元细胞迁移相关基因的表达与NURR1表达密切相关，而细胞周期进程与其负相关，精确地概括了中脑多巴胺能的发育。总的来说,对NURR1控制的调节网络的系统检查提供了对该蛋白在基于多巴胺的神经发生中的生物学功能的重要见解。
