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Cytosine epigenetic modification modulates the formation of an unprecedented G4 structure in the WNT1 promoter.
Nucleic Acids Research ( IF 16.6 ) Pub Date : 2020-01-08 , DOI: 10.1093/nar/gkz1207
Zi-Fu Wang,Ming-Hao Li,I-Te Chu,Fernaldo R Winnerdy,Anh T Phan,Ta-Chau Chang

Time-resolved imino proton nuclear magnetic resonance spectra of the WT22m sequence d(GGGCCACCGGGCAGTGGGCGGG), derived from the WNT1 promoter region, revealed an intermediate G-quadruplex G4(I) structure during K+-induced conformational transition from an initial hairpin structure to the final G4(II) structure. Moreover, a single-base C-to-T mutation at either position C4 or C7 of WT22m could lock the intermediate G4(I) structure without further conformational change to the final G4(II) structure. Surprisingly, we found that the intermediate G4(I) structure is an atypical G4 structure, which differs from a typical hybrid G4 structure of the final G4(II) structure. Further studies of modified cytosine analogues associated with epigenetic regulation indicated that slight modification on a cytosine could modulate G4 structure. A simplified four-state transition model was introduced to describe such conformational transition and disclose the possible mechanism for G4 structural selection caused by cytosine modification.

中文翻译:

胞嘧啶表观遗传修饰调节WNT1启动子中前所未有的G4结构的形成。

从WNT1启动子区域衍生的WT22m序列d(GGGCCACCGGGCAGTGGGGGGGGG)的时间分辨亚氨基质子核磁共振谱揭示了在K +诱导的构象转变过程中,G +四联体G4(I)是中间结构,从最初的发夹结构到最终的发夹结构G4(II)结构。此外,WT22m的位置C4或C7处的单碱基C到T突变可以锁定中间G4(I)结构,而无需进一步改变最终G4(II)结构的构象。令人惊讶地,我们发现中间的G4(I)结构是非典型的G4结构,其不同于最终的G4(II)结构的典型杂化G4结构。与表观遗传调控相关的修饰胞嘧啶类似物的进一步研究表明,胞嘧啶的轻微修饰可以调节G4结构。
更新日期:2020-02-18
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