title: Discovery and Structural Characterization of G-quadruplex DNA in Human Acetyl-CoA Carboxylase Gene Promoters: Its Role in Transcriptional Regulation and as a Therapeutic Target for Human Disease.
abstract: Accumulating evidence suggests that G-quadruplexes play vital roles in gene expression, DNA replication, and recombination. Three distinct promoters (PI, PII, and PIII) regulate human acetyl-CoA carboxylase 1 (ACC1) gene expression. In this study, we asked whether the G-rich sequences within the human ACC1 (PI and PII) promoters can form G-quadruplex structures and regulate normal DNA transactions. Using multiple complementary methods, we show that G-rich sequences of PI and PII promoters form intramolecular G-quadruplex structures and then establish unambiguously the topologies of these structures. Importantly, G-quadruplex formation in ACC1 gene promoter region blocks DNA replication and suppresses transcription, and this effect was further augmented by G-quadruplex stabilizing ligands. Altogether, these results are consistent with the notion that G-quadruplex structures exist within the human ACC1 gene promoter region, whose activity can be suppressed by G-quadruplex stabilizing ligands, thereby revealing a novel regulatory mechanism of ACC1 gene expression and as a possible therapeutic target.
authors.forename: Mangesh
authors.initials: M
authors.lastname: Kaulage
authors.forename: Basudeb
authors.initials: B
authors.lastname: Maji
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Bhat
authors.affiliation: Department of Endocrinology, Metabolism, and Nephrology, Kochi Medical School, Kochi University , Nankoku 780-8520, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwasaki
authors.affiliation: Department of Biophysics, Bose Institute , Kolkata 700054, India.
authors.forename: Subhrangsu
authors.initials: S
authors.lastname: Chatterjee
authors.forename: Santanu
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: K
authors.initials: K
authors.lastname: Muniyappa
mesh_terms: D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D054856:G-Quadruplexes / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D009690:Nucleic Acid Conformation / Q000187:drug effects; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics*; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D008024:Ligands; D000103:Acetyl-CoA Carboxylase