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一种利用果蝇鉴定异染色质促进药物的筛选方法。

A Screening Method for Identification of Heterochromatin-Promoting Drugs Using Drosophila.

作者信息

Zhang Lin, Dao Kenny, Kang Angela, Loyola Andre C, Shang Robin, Li Jinghong, Li Willis X

机构信息

Department of Medicine, University of California San Diego;

Department of Medicine, University of California San Diego.

出版信息

J Vis Exp. 2020 Mar 12(157). doi: 10.3791/60917.

Abstract

Drosophila is an excellent model organism that can be used to screen compounds that might be useful for cancer therapy. The method described here is a cost-effective in vivo method to identify heterochromatin-promoting compounds by using Drosophila. The Drosophila's DX1 strain, having a variegated eye color phenotype that reflects the extents of heterochromatin formation, thereby providing a tool for a heterochromatin-promoting drug screen. In this screening method, eye variegation is quantified based on the surface area of red pigmentation occupying parts of the eye and is scored on a scale from 1 to 5. The screening method is straightforward and sensitive and allows for testing compounds in vivo. Drug screening using this method provides a fast and inexpensive way for identifying heterochromatin-promoting drugs that could have beneficial effects in cancer therapeutics. Identifying compounds that promote the formation of heterochromatin could also lead to the discovery of epigenetic mechanisms of cancer development.

摘要

果蝇是一种优秀的模式生物,可用于筛选可能对癌症治疗有用的化合物。这里描述的方法是一种经济高效的体内方法,通过使用果蝇来鉴定促进异染色质形成的化合物。果蝇的DX1品系具有反映异染色质形成程度的斑驳眼色表型,从而为促进异染色质的药物筛选提供了一种工具。在这种筛选方法中,根据占据眼睛部分区域的红色色素沉着的表面积对眼睛斑驳程度进行量化,并按1至5的等级评分。该筛选方法简单且灵敏,允许在体内测试化合物。使用这种方法进行药物筛选为鉴定可能对癌症治疗有有益作用的促进异染色质形成的药物提供了一种快速且廉价的方式。鉴定促进异染色质形成的化合物也可能导致发现癌症发展的表观遗传机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bdd8/7323709/7de33b824d55/nihms-1589957-f0001.jpg

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Mol Cell. 2018 Jun 7;70(5):842-853.e7. doi: 10.1016/j.molcel.2018.04.023. Epub 2018 May 31.
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Nat Rev Mol Cell Biol. 2018 Apr;19(4):229-244. doi: 10.1038/nrm.2017.119. Epub 2017 Dec 13.
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