Frontiers in Microbiology (Nov 2017)

Characterization of a Suppressive Cis-acting Element in the Epstein–Barr Virus LMP1 Promoter

  • Masahiro Yoshida,
  • Takayuki Murata,
  • Takayuki Murata,
  • Keiji Ashio,
  • Yohei Narita,
  • Takahiro Watanabe,
  • H. M. Abdullah Al Masud,
  • Yoshitaka Sato,
  • Fumi Goshima,
  • Hiroshi Kimura

DOI
https://doi.org/10.3389/fmicb.2017.02302
Journal volume & issue
Vol. 8

Abstract

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Latent membrane protein 1 (LMP1) is a major oncogene encoded by Epstein–Barr virus (EBV) and is essential for immortalization of B cells by the virus. Previous studies suggested that several transcription factors, such as PU.1, RBP-Jκ, NFκB, EBF1, AP-2 and STAT, are involved in LMP1 induction; however, the means by which the oncogene is negatively regulated remains unclear. Here, we introduced short mutations into the proximal LMP1 promoter that includes recognition sites for the E-box and Ikaros transcription factors in the context of EBV-bacterial artificial chromosome. Upon infection, the mutant exhibited increased LMP1 expression and EBV-mediated immortalization of B cells. However, single mutations of either the E-box or Ikaros sites had limited effects on LMP1 expression and transformation. Our results suggest that this region contains a suppressive cis-regulatory element, but other transcriptional repressors (apart from the E-box and Ikaros transcription factors) may remain to be discovered.

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