The role of Dichaete in transcriptional regulation during Drosophila embryonic development.
The role of Dichaete in transcriptional regulation during Drosophila embryonic development.
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DOI：
10.1186/1471-2164-14-861
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发表时间：
2013-12-08
期刊：
影响因子：
4.4
通讯作者：
Russell S
中科院分区：
文献类型：
--
作者：
Aleksic J;Ferrero E;Fischer B;Shen SP;Russell S
B组Sox结构域转录因子在高等后生动物神经系统的规范和发育中起着保守的作用。然而，我们对这些转录因子如何调控基因表达知之甚少，而且SOX基因在脊椎动物中的功能分析被三个密切相关的家族成员之间的功能补偿所混淆。在果蝇中，只有两个B组Sox基因，Dichaete和SoxN，被证明在胚胎中枢神经系统发育过程中发挥作用，这为理解这一重要类别的调节因子的功能提供了一个更简单的系统。结合转录图谱和全基因组结合分析，我们保守地鉴定了果蝇基因组中1000多个高置信度的直接Dichaete靶基因。我们发现Dichaete在中枢神经系统发育中起着关键作用，它调节着赋予神经母细胞特性的时间转录因子序列的某些方面。Dichaete还在控制干细胞自我更新到神经分化的转换过程中与Propero表现出复杂的相互作用。Dichaete潜在地调节果蝇基因组中更多的基因，并被发现与2000多个定位的调节元件有关。我们的分析表明，Dichaete作为转录中心，在中枢神经系统发育过程中控制着多条调控途径。这些基因包括一组中枢神经系统核心表达基因，在哺乳动物中枢神经系统发育过程中也与相关的Sox2基因结合。此外，我们确定Dichaete是参与神经干细胞转录网络的转录因子之一，有证据支持Dichaete参与控制调节神经母细胞身份的时间序列分裂。
Group B Sox domain transcription factors play conserved roles in the specification and development of the nervous system in higher metazoans. However, we know comparatively little about how these transcription factors regulate gene expression, and the analysis of Sox gene function in vertebrates is confounded by functional compensation between three closely related family members. In Drosophila, only two group B Sox genes, Dichaete and SoxN, have been shown to function during embryonic CNS development, providing a simpler system for understanding the functions of this important class of regulators. Using a combination of transcriptional profiling and genome-wide binding analysis we conservatively identify over 1000 high confidence direct Dichaete target genes in the Drosophila genome. We show that Dichaete plays key roles in CNS development, regulating aspects of the temporal transcription factor sequence that confer neuroblast identity. Dichaete also shows a complex interaction with Prospero in the pathway controlling the switch from stem cell self-renewal to neural differentiation. Dichaete potentially regulates many more genes in the Drosophila genome and was found to be associated with over 2000 mapped regulatory elements. Our analysis suggests that Dichaete acts as a transcriptional hub, controlling multiple regulatory pathways during CNS development. These include a set of core CNS expressed genes that are also bound by the related Sox2 gene during mammalian CNS development. Furthermore, we identify Dichaete as one of the transcription factors involved in the neural stem cell transcriptional network, with evidence supporting the view that Dichaete is involved in controlling the temporal series of divisions regulating neuroblast identity.
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