Journal
NUCLEIC ACIDS RESEARCH
Volume 48, Issue 3, Pages 1120-1130Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkz1207
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Funding
- Academia Sinica [AS-102-TPA07]
- Ministry of Science and Technology of the Republic of China [MOST-106-2119-M-001-030-MY3]
- Singapore National Research Foundation Investigatorship [NRF-NRFI2017-09]
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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 C-4 or C-7 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.
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