title: Investigation on the formation, conversion and bioactivity of a G-quadruplex structure in the PALB2 gene.
abstract: There is a putative G-quadruplex sequence (PGS), 5'-G3ACAG4TTG2TG4 TAG4CAG2TTG3-3', in the promoter region of the PALB2 gene. According to the importance of PALB2 in the process of homologous recombination and breast cancer, and the hypothesis that G-quadruplexes might play a role in transcriptional regulation, we evaluated the formation of G-quadruplex from this complex sequence, as well as its structural information and importance for PALB2 transcription. The G-rich sequence was suggested to form G-quadruplex structure in the NH4OAc solution with 3NH4+ ion by ESI-MS spectrometry, and it was testified in the KCl solution by CD experiments which showed the typical 290 nm band and a high melting temperature. We also classified the guanines in the sequence into four types and demonstrated their roles in the formation of the G-quadruplex structure. In addition, a luciferase assay proved that the formation of the G-quadruplex down-regulate the transcription of the gene. Therefore, our findings provided a foundation for the formation and bioactivity of the G-quadruplex in the promoter region of PALB2 gene and a novel insight for understanding PALB2 gene regulation.
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Fangyuan
authors.initials: F
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China. Electronic address: zhoujiang@pku.edu.cn.
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Institute of Vascular Medicine, Department of Cardiology, Peking University Third Hospital, Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Ministry of Health, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Yuan
mesh_terms: D001483:Base Sequence; D000076164:Fanconi Anemia Complementation Group N Protein; D054856:G-Quadruplexes; D005786:Gene Expression Regulation; D006801:Humans; D061986:MCF-7 Cells; D009687:Nuclear Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D014158:Transcription, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins
keywords: ESI-MS; G-quadruplex; PALB2 gene