Conformation Selective Antibody Enables Genome Profiling and Leads to Discovery of Parallel G-Quadruplex in Human Telomeres.
G-quadruplexes are specialized secondary structures in nucleic acids that possess significant conformational polymorphisms. The precise G-quadruplex conformations in vivo and their relevance to biological functions remain controversial and unclear, especially for telomeric G-quadruplexes. Here, we report a novel single-chain variable fragment (scFv) antibody, D1, with high binding selectivity for parallel G-quadruplexes in vitro and in vivo. Genome-wide chromatin immunoprecipitation using D1 and deep-sequencing revealed the consensus sequence for parallel G-quadruplex formation, which is characterized by G-rich sequence with a short loop size (<3 nt). By using D1, telomeric parallel G-quadruplex was identified and its formation was regulated by small molecular ligands targeting and telomere replication. Together, parallel G-quadruplex specific antibody D1 was found to be a valuable tool for determination of G-quadruplex and its conformation, which will prompt further studies on the structure of G-quadruplex and its biological implication in vivo.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Hui-Yun
HY
Liu
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Qi
Q
Zhao
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Tian-Peng
TP
Zhang
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Yue
Y
Wu
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Yun-Xia
YX
Xiong
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Shi-Ke
SK
Wang
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Yuan-Long
YL
Ge
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Jin-Hui
JH
He
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Peng
P
Lv
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China. Electronic address: outianm@mail.sysu.edu.cn.
Tian-Miao
TM
Ou
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Jia-Heng
JH
Tan
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Ding
D
Li
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Lian-Quan
LQ
Gu
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China.
Jian
J
Ren
School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China. Electronic address: zhaoy82@mail.sysu.edu.cn.
Yong
Y
Zhao
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, P.R. China. Electronic address: ceshzs@mail.sysu.edu.cn.
Zhi-Shu
ZS
Huang
D001483:Base Sequence; D002460:Cell Line; D016384:Consensus Sequence; D054856:G-Quadruplexes; D015894:Genome, Human; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D057127:Single-Chain Antibodies / Q000737:chemistry* / Q000276:immunology; D016615:Telomere / Q000737:chemistry* / Q000235:genetics / Q000276:immunology
D008024:Ligands; D057127:Single-Chain Antibodies
antibody; conformational selectivity; consensus sequence; parallel G-quadruplex; telomeric G-quadruplex