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首页> 外文期刊>Neuron >Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons
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Transcriptional Networks Controlled by NKX2-1 in the Development of Forebrain GABAergic Neurons

机译：NKX2-1控制的前脑GABA能神经元发育中的转录网络。

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The embryonic basal ganglia generates multiple projection neurons and interneuron subtypes from distinct progenitor domains. Combinatorial interactions of transcription factors and chromatin are thought to regulate gene expression. In the medial ganglionic eminence, the NKX2-1 transcription factor controls regional identity and, with LHX6, is necessary to specify pallidal projection neurons and fore-brain interneurons. Here, we dissected the molecular functions of NKX2-1 by defining its chromosomal binding, regulation of gene expression, and epigenetic state. NKX2-1 binding at distal regulatory elements led to a repressed epigenetic state and transcriptional repression in the ventricular zone. Conversely, NKX2-1 is required to establish a permissive chromatin state and transcriptional activation in the sub-ventricular and mantle zones. Moreover, combinatorial binding of NKX2-1 and LHX6 promotes transcriptionally permissive chromatin and activates genes expressed in cortical migrating interneurons. Our integrated approach provides a foundation for elucidating transcriptional networks guiding the development of the MGE and its descendants.
机译：胚胎基底神经节从不同的祖细胞域产生多个投射神经元和中间神经元亚型。转录因子和染色质的组合相互作用被认为调节基因表达。在内侧神经节突起中，NKX2-1转录因子控制区域同一性，并且与LHX6一起用于指定苍白球投射神经元和前脑神经元。在这里，我们通过定义NKX2-1的染色体结合，基因表达的调控和后生状态来剖析其分子功能。 NKX2-1在远端调控元件上的结合导致心室区的表观遗传状态和转录抑制。相反，需要NKX2-1在心室下和外套膜区建立允许的染色质状态和转录激活。此外，NKX2-1和LHX6的组合结合促进转录许可的染色质并激活在皮层迁移的中间神经元中表达的基因。我们的综合方法为阐明指导MGE及其后代发展的转录网络提供了基础。

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