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首页> 外文期刊>Molecular and Cellular Biology >GATA factors are essential for activity of the neuron-specific enhancer of the gonadotropin-releasing hormone gene.
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GATA factors are essential for activity of the neuron-specific enhancer of the gonadotropin-releasing hormone gene.

机译:GATA因子对于促性腺激素释放激素基因的神经元特异性增强子的活性至关重要。

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The multicomponent neuron-specific enhancer of the gonadotropin-releasing hormone (GnRH) gene specifically targets expression to the GnRH-secreting neurons of the hypothalamus, a small population of specialized cells which play a central role in regulating reproductive function. Utilizing the GnRH-secreting hypothalamic neuronal cell line, GT1, as a model system, we show that members of the GATA family of transcription factors regulate GnRH transcription through two GATA factor-binding motifs that occur in a tandem repeat within the GnRH neuron-specific enhancer. Although GT1 cells contain GATA-2 and GATA-4 mRNAs, only GATA-4 was detected in a GnRH enhancer GATA site-specific complex. Cotransfection experiments with wild-type and mutant GnRH enhancer reporter plasmids with wild-type and dominant negative GATA factor expression vectors demonstrated that both GATA-binding elements are functional in the context of the enhancer. We conclude that GATA-binding proteins are important factors in regulating the neuron-specific expression of the GnRH gene in hypothalamic cells. Although the presence of GATA-2 in a neuronal cell type is not unusual, the presence of GATA-4 in GT1 cells is novel for a neuronal cell type. However, the presence of GATA-4 is consistent with the unique developmental origin of GnRH neurons and may provide insight into the transcriptional mechanisms mediating the differentiation of this limited population of GnRH-secreting neurons.
机译:促性腺激素释放激素(GnRH)基因的多组分神经元特异性增强子特异性地靶向下丘脑分泌GnRH的神经元的表达,下丘脑是少数专门细胞,在调节生殖功能中起着重要作用。利用分泌GnRH的下丘脑神经元细胞系GT1作为模型系统,我们表明,转录因子GATA家族成员通过在GnRH神经元特异的串联重复序列中出现的两个GATA因子结合基序调节GnRH转录。增强剂。尽管GT1细胞包含GATA-2和GATA-4 mRNA,但在GnRH增强剂GATA位点特异性复合物中仅检测到GATA-4。野生型和突变型GnRH增强子报告质粒与野生型和显性负GATA因子表达载体的共转染实验表明,两种GATA结合元件在增强子的背景下均具有功能。我们得出结论,GATA结合蛋白是调节下丘脑细胞中GnRH基因神经元特异性表达的重要因素。尽管神经元细胞类型中GATA-2的存在并不罕见,但对于神经元细胞类型,GT1细胞中GATA-4的存在是新颖的。但是,GATA-4的存在与GnRH神经元的独特发育起源是一致的,并且可以提供对介导此GnRH分泌神经元有限种群分化的转录机制的深入了解。

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