title: Stabilization of G-quadruplex DNA by C-5-methyl-cytosine in bcl-2 promoter: implications for epigenetic regulation.
abstract: The C-5-methylation of cytosine in the CpG islands is an important pattern for epigenetic modification of gene, which plays a key role in regulating gene transcription. G-quadruplex is an unusual DNA secondary structure formed in G-rich regions and is identified as a transcription repressor in some oncogenes, such as c-myc and bcl-2. In the present study, the results from CD spectrum and FRET assay showed that the methylation of cytosine in the CpG islands could induce a conformational change of the G-quadruplex in the P1 promoter of bcl-2, and greatly increase the thermal-stability of this DNA oligomer. Moreover, the methylation of cytosine in the G-quadruplex could protect the structure from the disruption by the complementary strand, showing with the increasing ability to arrest the polymerase in PCR stop assay. This data indicated that the stabilization of the G-quadruplex structure in the CpG islands might be involved in the epigenetical transcriptional regulation for specific genes through the C-5-methylation modification pattern.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lin
authors.forename: Jin-qiang
authors.initials: JQ
authors.lastname: Hou
authors.forename: Han-dan
authors.initials: HD
authors.lastname: Xiang
authors.forename: Yi-yong
authors.initials: YY
authors.lastname: Yan
authors.forename: Yu-chao
authors.initials: YC
authors.lastname: Gu
authors.forename: Jia-heng
authors.initials: JH
authors.lastname: Tan
authors.forename: Ding
authors.initials: D
authors.lastname: Li
authors.forename: Lian-quan
authors.initials: LQ
authors.lastname: Gu
authors.forename: Tian-miao
authors.initials: TM
authors.lastname: Ou
authors.forename: Zhi-shu
authors.initials: ZS
authors.lastname: Huang
mesh_terms: D002942:Circular Dichroism; D019295:Computational Biology / Q000379:methods; D018899:CpG Islands; D003596:Cytosine / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D019254:Genes, bcl-2; D006801:Humans; D008958:Models, Molecular; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction / Q000379:methods; D011401:Promoter Regions, Genetic; D013696:Temperature; D014158:Transcription, Genetic
chemical_list: D003596:Cytosine