Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in Drosophila
Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in Drosophila
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DOI：
10.15252/embj.201798659
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发表时间：
2018-07
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影响因子：
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通讯作者：
Katja Rust;Manu D. Tiwari;V. Mishra;F. Grawe;A. Wodarz
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作者：
Katja Rust;Manu D. Tiwari;V. Mishra;F. Grawe;A. Wodarz
干细胞建立皮层极性并进行不对称分裂，同时维持自身并产生分化的后代细胞。在哺乳动物多能干细胞中，已经发现了几种染色质修饰因子作为干细胞性因子，但这些因子是否控制干细胞极性和不对称分裂尚未得到研究。我们在果蝇神经干细胞中解决了这个问题，称为神经母细胞。我们确定了Tip60染色质重塑复合体及其相互作用伙伴Myc作为神经母细胞维持所需基因的调节因子。敲低Tip60复合体成员会导致皮质极性丧失，神经母细胞分裂对称，以及通过转录因子普洛斯彼罗进入细胞核而过早分化。我们发现aPKC是Myc和Tip60复合物亚基Domino调控神经母细胞极性的关键靶基因。我们的转录组分析进一步表明，Domino调节有丝分裂纺锤体基因的表达，这些基因先前被认为是Myc的直接靶点。我们的研究结果揭示了Myc、Tip60复合体和控制细胞极性和不对称细胞分裂的分子网络之间存在进化上保守的功能联系。
Stem cells establish cortical polarity and divide asymmetrically to simultaneously maintain themselves and generate differentiating offspring cells. Several chromatin modifiers have been identified as stemness factors in mammalian pluripotent stem cells, but whether these factors control stem cell polarity and asymmetric division has not been investigated so far. We addressed this question in Drosophila neural stem cells called neuroblasts. We identified the Tip60 chromatin remodeling complex and its interaction partner Myc as regulators of genes required for neuroblast maintenance. Knockdown of Tip60 complex members results in loss of cortical polarity, symmetric neuroblast division, and premature differentiation through nuclear entry of the transcription factor Prospero. We found that aPKC is the key target gene of Myc and the Tip60 complex subunit Domino in regulating neuroblast polarity. Our transcriptome analysis further showed that Domino regulates the expression of mitotic spindle genes previously identified as direct Myc targets. Our findings reveal an evolutionarily conserved functional link between Myc, the Tip60 complex, and the molecular network controlling cell polarity and asymmetric cell division.