title: Yin Yang 1 contains G-quadruplex structures in its promoter and 5'-UTR and its expression is modulated by G4 resolvase 1.
abstract: Yin Yang 1 (YY1) is a multifunctional protein with regulatory potential in tumorigenesis. Ample studies demonstrated the activities of YY1 in regulating gene expression and mediating differential protein modifications. However, the mechanisms underlying YY1 gene expression are relatively understudied. G-quadruplexes (G4s) are four-stranded structures or motifs formed by guanine-rich DNA or RNA domains. The presence of G4 structures in a gene promoter or the 5'-UTR of its mRNA can markedly affect its expression. In this report, we provide strong evidence showing the presence of G4 structures in the promoter and the 5'-UTR of YY1. In reporter assays, mutations in these G4 structure forming sequences increased the expression of Gaussia luciferase (Gluc) downstream of either YY1 promoter or 5'-UTR. We also discovered that G4 Resolvase 1 (G4R1) enhanced the Gluc expression mediated by the YY1 promoter, but not the YY1 5'-UTR. Consistently, G4R1 binds the G4 motif of the YY1 promoter in vitro and ectopically expressed G4R1 increased endogenous YY1 levels. In addition, the analysis of a gene array data consisting of the breast cancer samples of 258 patients also indicates a significant, positive correlation between G4R1 and YY1 expression.
authors: Department of Cancer Biology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors: Weiwei
authors: W
authors: Huang
authors: Philip J
authors: PJ
authors: Smaldino
authors: Qiang
authors: Q
authors: Zhang
authors: Lance D
authors: LD
authors: Miller
authors: Paul
authors: P
authors: Cao
authors: Kristin
authors: K
authors: Stadelman
authors: Meimei
authors: M
authors: Wan
authors: Banabihari
authors: B
authors: Giri
authors: Ming
authors: M
authors: Lei
authors: Yoshikuni
authors: Y
authors: Nagamine
authors: James P
authors: JP
authors: Vaughn
authors: Steven A
authors: SA
authors: Akman
authors: Guangchao
authors: G
authors: Sui
mesh_terms: D020121:5' Untranslated Regions; D001483:Base Sequence; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D002414:Cations, Monovalent / Q000737:chemistry; D002460:Cell Line; D002942:Circular Dichroism; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D018983:DNA Footprinting; D005260:Female; D054856:G-Quadruplexes; D020862:GC Rich Sequence; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D011401:Promoter Regions, Genetic; D012313:RNA / Q000737:chemistry; D045522:Recombinases / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000235:genetics* / Q000378:metabolism
chemical_list: D020121:5' Untranslated Regions; D002414:Cations, Monovalent; D009838:Oligodeoxyribonucleotides; D045522:Recombinases; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; D012313:RNA; D004247:DNA; C466988:DHX36 protein, human; D053487:DEAD-box RNA Helicases