Ascl1 represses the mesendoderm induction in Xenopus
Ascl1 represses the mesendoderm induction in Xenopus
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Ascl1 抑制爪蟾中内胚层诱导
DOI：
10.1093/abbs/gmw092
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发表时间：
2016
影响因子：
3.7
通讯作者：
Tao Qinghua
中科院分区：
文献类型：
--
作者：
Min Zheying;Lin Hao;Zhu Xuechen;Gao Li;Kh;Aftab A;Tao Qinghua
Ascl 1是无脊椎动物和脊椎动物神经发育的多功能调节因子。Ascl 1的异位表达可以从非神经体细胞产生功能性神经元。ASCL 1的异常表达已被报道在几种类型的癌症。我们以前已经确定Ascl 1作为一个至关重要的母系调节器的胚层模式形成inXenopus。功能研究表明，母亲提供的Ascl 1使胚胎细胞倾向于采用神经命运，并抑制中内胚层形成的另一方面。然而，目前尚不清楚Ascl 1如何实现其阻遏物功能的中内胚层基因的VegT激活。在此，我们进行了一系列的功能获得和功能丧失实验，发现：（i）VegT是非洲爪蟾中的母体中内胚层决定子，在中内胚层诱导过程中，VegT是H3 K27 ac和H3 K9 ac在其靶基因位点沉积所必需的：（ii）Ascl 1和VegT拮抗性调节乙酰化组蛋白标记在中内胚层基因位点的沉积;（iii）Ascl 1过表达降低了中内胚层基因位点的VegT占据率;（iv）Ascl 1而不是Neurog 2在中内胚层诱导期间具有抑制活性。这些发现揭示了Ascl 1在早期异种胚胎发生过程中抑制非神经命运的一种新的抑制功能。
Ascl1 is a multi-functional regulator of neural development in invertebrates and vertebrates. Ectopic expression of Ascl1 can generate functional neurons from non-neural somatic cells. The abnormal expression of ASCL1 has been reported in several types of carcinomas. We have previously identified Ascl1 as a crucial maternal regulator of the germ layer pattern formation inXenopus. Functional studies have indicated that the maternally-supplied Ascl1 renders embryonic cells a propensity to adopt neural fates on one hand, and represses the mesendoderm formation on the other. However, it remains unclear how Ascl1 achieves its repressor function during the activation of mesendoderm genes by VegT. Here, we performed series of gain- and loss-of-function experiments and found that: (i) VegT, the maternal mesendoderm determinant inXenopus, is required for the deposition of H3K27ac and H3K9ac at its target gene loci during mesendoderm induction; (ii) Ascl1 and VegT antagonistically modulate the deposition of acetylated histone marks at mesendoderm gene loci; (iii) Ascl1 overexpression reduces the VegT-occupancy at mesendoderm gene loci; (iv) Ascl1 but not Neurog2 possesses a repressive activity during mesendoderm induction. These findings reveal a novel repressive function for Ascl1 in inhibiting non-neural fates during earlyXenopusembryogenesis.