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脂肪通过一个 20 碱基对的元件独立于 Hippo 通路调节体内四关节报告基因的表达。

Fat regulates expression of four-jointed reporters in vivo through a 20 bp element independently of the Hippo pathway.

机构信息

Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, Toronto, Canada.

Department of Developmental Biology, Washington University School of Medicine, St. Louis, MO, USA.

出版信息

Dev Biol. 2019 Jun 1;450(1):23-33. doi: 10.1016/j.ydbio.2019.03.004. Epub 2019 Mar 9.

Abstract

Development of an organism requires accurate coordination between the growth of a tissue and orientation of cells within the tissue. The large cadherin Fat has been shown to play a role in both of these processes. Fat is involved in the establishment of planar cell polarity and regulates growth through the Hippo pathway, a developmental cascade that controls proliferation and apoptosis. Both Fat and the Hippo pathway are known to regulate transcription of four-jointed, although the nature of this regulation is unknown. In this study, we test whether Fat affects four-jointed transcription via or independently of Hippo pathway. Our analysis of the four-jointed regulatory region reveals a 1.2 kb element that functions as an enhancer for graded expression of Four-jointed in the eye imaginal disc. Within this enhancer element, we identify a 20 bp fragment that is critical for regulation by Fat but not by Hippo. Our findings suggest that Fat and the Hippo pathway control four-jointed expression independently of each other and none of the transcription factors known to function downstream of the Hippo pathway are required to regulate four-jointed expression through the 1.2 kb element.

摘要

生物体的发育需要组织的生长和组织内细胞的定向之间的精确协调。大型钙粘蛋白 Fat 已被证明在这两个过程中都发挥作用。Fat 参与平面细胞极性的建立,并通过 Hippo 途径调节生长,Hippo 途径是一种控制增殖和细胞凋亡的发育级联。Fat 和 Hippo 途径都已知调节 Four-jointed 的转录,尽管这种调节的性质尚不清楚。在这项研究中,我们测试 Fat 是否通过 Hippo 途径或独立于 Hippo 途径影响 Four-jointed 的转录。我们对 Four-jointed 调节区的分析揭示了一个 1.2kb 的元件,该元件作为眼部 imaginal disc 中 Four-jointed 梯度表达的增强子发挥作用。在这个增强子元件内,我们确定了一个 20bp 的片段,该片段对于 Fat 的调节至关重要,但对于 Hippo 的调节则不重要。我们的研究结果表明,Fat 和 Hippo 途径独立地控制 Four-jointed 的表达,并且已知在 Hippo 途径下游发挥作用的转录因子都不需要通过 1.2kb 元件来调节 Four-jointed 的表达。

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