Yin Yang 1 contains G-quadruplex structures in its promoter and 5′-UTR and its expression is modulated by G4 resolvase 1

Weiwei Huang, Philip J. Smaldino, Qiang Zhang, Lance D. Miller, Paul Cao, Kristin Stadelman, Meimei Wan, Banabihari Giri, Ming Lei, Yoshikuni Nagamine, James P. Vaughn, Steven A. Akman, Guangchao Sui

Research output: Contribution to journalArticle

58 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1033-1049
Number of pages17
JournalNucleic Acids Research
Volume40
Issue number3
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics

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    Huang, W., Smaldino, P. J., Zhang, Q., Miller, L. D., Cao, P., Stadelman, K., Wan, M., Giri, B., Lei, M., Nagamine, Y., Vaughn, J. P., Akman, S. A., & Sui, G. (2012). Yin Yang 1 contains G-quadruplex structures in its promoter and 5′-UTR and its expression is modulated by G4 resolvase 1. Nucleic Acids Research, 40(3), 1033-1049. https://doi.org/10.1093/nar/gkr849