試想如果我們通過拉拽電燈開關就可以輕松控制基因的表達,，這將是一件多么神奇的事情,；近日,，來自北卡羅來納大學的研究者成功運用了光敏分子來控制基因的表達，研究者的這種方法可以高精度地研究基因的功能,，而且對于諸如癌癥等疾病可以開展靶向治療,。
三股螺旋形式的寡核苷酸類（TFOs）分子通常通過結合在雙股DNA上來阻止基因的轉(zhuǎn)錄，研究者Alex Deiters試圖找到一種更為精準的方法來控制TFOs,，并且使得控制的范圍延伸至特定基因的轉(zhuǎn)錄,。因此研究者設計了一種光敏支架來吸附到TFO上，當這種光敏支架暴露于紫外光下就會移動,，此時,，TFO便可以自由結合在DNA上，抑制特定基因的轉(zhuǎn)錄,。
如果沒有光的話,，基因的轉(zhuǎn)錄活性為100%，但是,，一旦有光的話,，研究者就可以使得目的基因的轉(zhuǎn)錄效率降至25%，這對于基因的表達量來說是一個明顯的降低,。
此外,，研究者Deiters優(yōu)化了光敏支架吸附到TFO上的過程，在沒有紫外線的時候,，TFO行使正常功能,，可以結合至DNA上抑制基因的表達；當暴露在紫外線下后,，光敏支架抑制TFO,，阻止TFO結合在DNA上，最終開啟基因的表達,。
研究者表示,，他們開發(fā)出的這種通過光敏開關來控制基因的遺傳轉(zhuǎn)錄的方法給很多科學家研究基因功能帶來了便利，可以讓科學家更為立體的控制基因的表達,，這樣一來,，我們不管在什么環(huán)境中都可以對特定基因的功能進行研究學習。
這項研究成果刊登在了近日的國際雜志ACS Chemical Biology上,，研究經(jīng)費由國立衛(wèi)生研究院支持,。（生物谷：T.Shen編譯）
doi:10.1021/cb300161r
PMC:
PMID:
Regulation of Transcription through Light-Activation and Light-Deactivation of Triplex-Forming Oligonucleotides in Mammalian Cells
Jeane Govan, Rajendra Uprety, James Hemphill, Mark O. Lively, and Alexander Deiters
Triplex-forming oligonucleotides (TFOs) are efficient tools to regulate gene expression through the inhibition of transcription. Here, nucleobase-caging technology was applied to the first temporal regulation of transcription through light-activated TFOs. Through site-specific incorporation of caged thymidine nucleotides, the TFO:DNA triplex formation is blocked, rendering the TFO inactive. However, after a brief UV irradiation, the caging groups are removed, activating the TFO, and leading to the inhibition of gene transcription. Furthermore, the synthesis and site-specific incorporation of caged deoxycytidine nucleotides within TFO inhibitor sequences was developed, and allows for the light-deactivation of TFO function and thus photochemical activation of gene expression. After UV-induced removal of the caging groups, the TFO forms a DNA dumbbell structure, rendering it inactive, releasing it from the DNA, and activating transcription. These are the first examples of light-regulated TFOs and their application in the photochemical activation and deactivation of gene expression. In addition, hairpin loop structures were found to significantly increase the efficacy of phosphodiester DNA-based TFOs in tissue culture
