Functional analysis of the evolutionarily conserved cis-regulatory elements on the sox17 gene in zebrafish
Functional analysis of the evolutionarily conserved cis-regulatory elements on the sox17 gene in zebrafish
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DOI：
10.1016/j.ydbio.2008.11.010
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发表时间：
2009-02-15
影响因子：
2.7
通讯作者：
Yuh, Chiou-Hwa
中科院分区：
文献类型：
--
作者：
Chan, Tzu-Min;Chao, Chung-Hao;Yuh, Chiou-Hwa
Sox 17是斑马鱼（Daniorerio）内胚层细胞的重要转录因子。根据GRNs的预测，基于扰动实验和文献检索，sox17基因与另外两个调控基因sox32和pou5f1接合。节点信号传导操作几个内胚层特异性转录因子，以确定内胚层规格。此外，内胚层特化需要FGF和Bmp信号传导途径在将成为内胚层的细胞中被抑制。推测Nodal激活sox32并与Pou5f1协同激活sox17，Bmp抑制sox17在腹侧的表达，Fgf抑制其在背侧的表达。sox17在基因组序列水平上的调控输入尚不清楚。在这里，我们已经发现了相关的sox17顺式调控元件，并检查了特定的输入预测的GRNs。我们发现了三个保守的模块，A，13和C，它们之间的协同效应。我们揭示了B模块上的Pou5f1结合元件和C模块上的Sox 32结合元件协同工作。此外，一个进化上不保守的R模块表现出抑制作用的腹侧和背侧。我们已经直接证明了在斑马鱼发育中内胚层GRNs的这个关键节点上基因组密码的结构和功能关系。这些信息为内胚层形成的复杂性提供了新的见解，并为建立完整的内胚层基因调控网络提供了宝贵的资源。(c)2008年爱思唯尔公司All rights reserved.
The Sox17 is an important transcription factor for endodermal cells (Danio rerio). According to the predictions of the GRNs, based on perturbation experiments and literature search, the sox17 gene is engaged with two other regulatory genes, sox32 and pou5f1. Nodal signaling operated on several endoderm-specific transcription factors to determine the endoderm specification. In addition, endoderm specification requires the Fgf and Bmp signaling pathways to be repressed in the cells which will become endoderm. It is predicted that Nodal activates sox32 and works synergistically with Pou5f1 to activate sox17 Bmp represses the expression of sox17 on the ventral side and Fgf represses it on the dorsal side. The regulatory inputs of sox17 at the genomic sequence level are not known. Here, we have uncovered the relevant sox17 cis-regulatory elements, and examined the specific input predictions of the GRNs. We discovered three conserved modules, A, 13, and C, with a synergistic effect among them. We revealed that the Pou5f1-binding element on the B module and the Sox32-binding element on the C module work synergistically. Furthermore, an evolutionarily non-conserved R module exhibits a repressive effect on both the ventral and dorsal side. We have directly demonstrated the structural and functional relationships of the genomic code at this key node of the endoderm GRNs in zebrafish development. This information provides new insight into the complexity of endoderm formation and serves as a valuable resource for the establishment of a complete endoderm gene regulatory network. (c) 2008 Elsevier Inc. All rights reserved.