Chan Tzu-Min, Chao Chung-Hao, Wang Horng-Dar, Yu Yen-Ju, Yuh Chiou-Hwa
Division of Molecular and Genomic Medicine, National Health Research Institutes, Taiwan, ROC.
Dev Biol. 2009 Feb 15;326(2):456-70. doi: 10.1016/j.ydbio.2008.11.010. Epub 2008 Nov 24.
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, B, 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.
Sox17是内胚层细胞(斑马鱼)的一种重要转录因子。根据基因调控网络(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相互作用。Nodal信号作用于几种内胚层特异性转录因子以确定内胚层特化。此外,内胚层特化要求在将成为内胚层的细胞中抑制Fgf和Bmp信号通路。据预测,Nodal激活sox32并与Pou5f1协同作用以激活sox17。Bmp在腹侧抑制sox17的表达,Fgf在背侧抑制它。sox17在基因组序列水平的调控输入尚不清楚。在此,我们发现了相关的sox17顺式调控元件,并检验了GRNs的特定输入预测。我们发现了三个保守模块,A、B和C,它们之间具有协同效应。我们揭示了B模块上的Pou5f1结合元件和C模块上的Sox32结合元件协同作用。此外,一个进化上不保守的R模块在腹侧和背侧均表现出抑制作用。我们直接证明了斑马鱼发育中内胚层GRNs这个关键节点处基因组编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资源。
Curr Biol. 1999-10-21
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