SP8 Transcriptional Regulation of Cyclin D1 During Mouse Early Corticogenesis
SP8 Transcriptional Regulation of Cyclin D1 During Mouse Early Corticogenesis
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DOI：
10.3389/fnins.2018.00119
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发表时间：
2018-03-02
影响因子：
4.3
通讯作者：
Dehay, Colette
中科院分区：
文献类型：
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作者：
Borello, Ugo;Berarducci, Barbara;Dehay, Colette
皮质生成过程中多种信号调控神经前体细胞增殖与分化的平衡。这种调节的关键点是G1期长度的控制，其由Cyclin/Cdks复合物调节。利用全基因组染色质免疫沉淀技术和小鼠遗传学方法，我们研究了细胞周期蛋白D1（Ccnd 1）在小鼠大脑皮层发育早期的转录调控。我们发现SP 8与外显子区域上的Ccnd 1位点结合的证据。体外实验表明，SP 8在Ccnd 1基因3 '端具有结合活性，并指出SP 8在调节PAX 6介导的Ccnd 1沿着发育中的腭板背腹轴的抑制中的假定作用，从而产生了神经元分化的中-低-侧-高梯度。Ccnd 1通过基因的启动子/5 '末端的激活不依赖于SP 8，而是依赖于B连环蛋白（CTNNB 1）。重要的是，体内Sp 8表达水平的改变影响早期皮质生成过程中Ccnd 1的表达。我们的研究结果表明，Ccnd 1调节是多个信号的结果，SP 8是这种调节的球员，揭示了一个意想不到的和潜在的新的转录激活机制。
Multiple signals control the balance between proliferation and differentiation of neural progenitor cells during corticogenesis. A key point of this regulation is the control of G1 phase length, which is regulated by the Cyclin/Cdks complexes. Using genome-wide chromatin immunoprecipitation assay and mouse genetics, we have explored the transcriptional regulation of Cyclin D1 (Ccnd1) during the early developmental stages of the mouse cerebral cortex. We found evidence that SP8 binds to the Ccnd1 locus on exon regions. In vitro experiments show SP8 binding activity on Ccnd1 gene 3 '-end, and point to a putative role for SP8 in modulating PAX6-mediated repression of Ccnd1 along the dorso-ventral axis of the developing pallium, creating a medialLow-lateralHigh gradient of neuronal differentiation. Activation of Ccnd1 through the promoter/5 '-end of the gene does not depend on SP8, but on b catenin (CTNNB1). Importantly, alteration of the Sp8 level of expression in vivo affects Ccnd1 expression during early corticogenesis. Our results indicate that Ccnd1 regulation is the result of multiple signals and that SP8 is a player in this regulation, revealing an unexpected and potentially novel mechanism of transcriptional activation.