Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation
Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation
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DOI：
10.1242/dev.00419
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发表时间：
2003-05-01
期刊：
影响因子：
4.6
通讯作者：
Johnson, JE
中科院分区：
文献类型：
--
作者：
Ebert, PJ;Timmer, JR;Johnson, JE
Math 1是一种在祖细胞中表达的碱性螺旋-环-螺旋转录因子，这些祖细胞产生脊髓背连合中间神经元、小脑颗粒细胞以及内耳和皮肤中的感觉细胞。在神经系统发育过程中，该基因的转录调控在时间和空间上都受到严格控制。介导这种调节的信号可能整合在Math 1增强子上，这在脊椎动物物种中是高度保守的。我们已经确定了锌指转录因子Zic 1作为Math 1表达的调节因子。Zic 1结合Math 1增强子内的一个新的保守位点，并抑制内源性Cath 1（Math 1的鸡同源物）的表达和Math 1增强子驱动的lacZ报告基因在鸡神经管中表达时的活性。Zic 1的抑制阻断了Math 1自身的自动调节活性。虽然以前的报道表明，Zic 1和Math 1都是由BMP信号诱导的，但这些基因似乎具有相反的功能，因为Math 1促进鸡神经管中的神经元分化，而过量的Zic 1似乎会阻止分化。Zic 1介导的Cath 1转录抑制可能调节神经管发育过程中祖细胞状态和分化背侧细胞类型之间的时间转换。
Math1 is a basic helix-loop-helix transcription factor expressed in progenitor cells that give rise to dorsal commissural interneurons in the spinal cord, granule cells of the cerebellum, and sensory cells in the inner ear and skin. Transcriptional regulation of this gene is tightly controlled both temporally and spatially during nervous system development. The signals that mediate this regulation are likely integrated at the Math1 enhancer, which is highly conserved among vertebrate species. We have identified the zinc-finger transcription factor Zic1 as a regulator of Math1 expression. Zic1 binds a novel conserved site within the Math1 enhancer, and represses both the expression of endogenous Cath1 (chicken homolog of Math1) and the activity of a Math1 enhancer driven lacZ reporter when expressed in chick neural tubes. Repression by Zic1 blocks the autoregulatory activity of Math1 itself. Although previous reports have shown that Zic1 and Math1 are both induced by BMP signaling, these genes appear to have opposing functions, as Math1 acts to promote neuronal differentiation in the chick neural tube and excess Zic1 appears to block differentiation. Zic1-mediated repression of Cath1 transcription may modulate the temporal switch between the progenitor state and differentiating dorsal cell types during neural tube development.