Activation of Xenopus genes required for lateral inhibition and neuronal differentiation during primary neurogenesis
Activation of Xenopus genes required for lateral inhibition and neuronal differentiation during primary neurogenesis
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DOI：
10.1006/mcne.1999.0783
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发表时间：
1999-10-01
影响因子：
3.5
通讯作者：
Kintner, C
中科院分区：
文献类型：
--
作者：
Koyano-Nakagawa, N;Wettstein, D;Kintner, C
XNGN-1是基本螺旋-环-螺旋蛋白神经原蛋白家族的成员，在非洲爪蟾胚胎中促进神经元分化起关键作用。当异位表达时，XNGN-1诱导神经元分化所需的一组基因的表达，如XMyT1和NeuroD。然而，与此同时，XNGN-1通过一种称为侧抑制的过程诱导拮抗神经元分化的基因表达。在这里，我们提供的证据表明，XNGN-1通过招募转录共激活因子p300/CBP （creb结合蛋白）或PCAF （p300/CBP相关蛋白）激活分化和侧向抑制所需基因的表达，这两种转录共激活因子都含有组蛋白乙酰转移酶（HAT）活性。值得注意的是，与介导分化的基因激活相比，侧抑制途径中基因的转录激活对HAT活性的依赖性较小。我们提出，这种差异使得侧抑制途径中的基因先于促进分化的基因被诱导，从而使侧抑制建立一个负反馈回路，并限制进行神经元分化的细胞数量。
XNGN-1, a member of the neurogenin family of basic helix-loop-helix proteins, plays a critical role in promoting neuronal differentiation in Xenopus embryos. When ectopically expressed, XNGN-1 induces the expression of a set of genes required for neuronal differentiation such as XMyT1 and NeuroD. At the same time, however, XNGN-1 induces the expression of genes that antagonize neuronal differentiation by a process called lateral inhibition. Here, we present evidence that XNGN-1 activates the expression of genes required for differentiation and lateral inhibition by recruiting transcriptional coactivators p300/CBP (CREB-binding protein) or PCAF (p300/CBP-associated protein), both of which contain histone acetyltransferase (HAT) activity. Significantly, transcriptional activation of the genes in the lateral inhibitory pathway is less dependent an the HAT activity than is the activation of the genes that mediate differentiation. We propose that this difference enables the genes in the lateral inhibition pathway to be induced prior to the genes that promote differentiation, thus enabling lateral inhibition to establish a negative feedback loop and restrict the number of cells undergoing neuronal differentiation.