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通过在DNA大沟中的光笼化、光释放和磷酸化反应，利用细菌RNA聚合酶进行转录切换。

Switching transcription with bacterial RNA polymerase through photocaging, photorelease and phosphorylation reactions in the major groove of DNA.

作者信息

Vaníková Zuzana, Janoušková Martina, Kambová Milada, Krásný Libor, Hocek Michal

机构信息

Institute of Organic Chemistry and Biochemistry , Czech Academy of Sciences , Flemingovo nam. 2 , 16610 Prague 6 , Czech Republic . Email:

Department of Organic Chemistry , Faculty of Science , Charles University in Prague , Hlavova 8 , CZ-12843 Prague 2 , Czech Republic.

出版信息

Chem Sci. 2019 Mar 4;10(14):3937-3942. doi: 10.1039/c9sc00205g. eCollection 2019 Apr 14.

DOI:10.1039/c9sc00205g
PMID:31015933
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6457204/
Abstract

We report proof of principle biomimetic switching of transcription through non-natural chemical reactions in the major groove of DNA templates. Photocaged DNA templates containing nitrobenzyl-protected 5-hydroxymethyluracil or - cytosine permitted no transcription with RNA polymerase (OFF state). Their irradiation with 400 nm light resulted in DNA templates containing hydroxymethylpyrimidines, which switched transcription ON with a higher yield (250-350%) compared to non-modified DNA. Phosphorylation of templates containing 5-hydroxymethyluracil (but not 5-hydroxymethylcytosine) then turned transcription OFF again. It is the first step towards artificial bioorthogonal chemical epigenetics.

摘要

我们报道了通过DNA模板大沟中的非天然化学反应进行转录的原理验证性仿生开关。含有硝基苄基保护的5-羟甲基尿嘧啶或5-羟甲基胞嘧啶的光笼DNA模板在RNA聚合酶作用下不发生转录（关闭状态）。用400nm光照射它们会产生含有羟甲基嘧啶的DNA模板，与未修饰的DNA相比，其转录开启的产量更高（250-350%）。然后，含有5-羟甲基尿嘧啶（而非5-羟甲基胞嘧啶）的模板磷酸化会再次使转录关闭。这是迈向人工生物正交化学表观遗传学的第一步。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/c46f2514c041/c9sc00205g-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/6341895f5270/c9sc00205g-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/bc88136007c7/c9sc00205g-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/e7585d61a263/c9sc00205g-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/bac6b2c27215/c9sc00205g-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/6a3e2346ef08/c9sc00205g-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/c46f2514c041/c9sc00205g-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/6341895f5270/c9sc00205g-s1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/bc88136007c7/c9sc00205g-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/e7585d61a263/c9sc00205g-s2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/bac6b2c27215/c9sc00205g-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/6a3e2346ef08/c9sc00205g-s3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c33/6457204/c46f2514c041/c9sc00205g-f3.jpg

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