Cytosine epigenetic modification modulates the formation of an unprecedented G4 structure in the WNT1 promoter 

March 24, 2020

Title

Cytosine epigenetic modification modulates the formation of an unprecedented G4 structure in the WNT1 promoter 

Author

Zi-Fu Wang, Ming-Hao Li, I-Te Chu, Fernaldo R Winnerdy, Anh T Phan, Ta-Chau Chang

Year

2020

Journal

Nucleic Acids Research

Abstract

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.

Instrument

J-815

Keywords

Circular dichroism, G-quadruplex structure, Chemical stability, Thermal stability, Biochemistry