Characterization of a suppressive Cis-acting element in the Epstein-Barr virus LMP1 promoter

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

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Abstract

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.

Original languageEnglish
Article number2302
JournalFrontiers in Microbiology
Volume8
Issue numberNOV
DOIs
Publication statusPublished - 22-11-2017

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All Science Journal Classification (ASJC) codes

  • Microbiology
  • Microbiology (medical)

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Yoshida, M., Murata, T., Ashio, K., Narita, Y., Watanabe, T., Al Masud, H. M. A., Sato, Y., Goshima, F., & Kimura, H. (2017). Characterization of a suppressive Cis-acting element in the Epstein-Barr virus LMP1 promoter. Frontiers in Microbiology, 8(NOV), [2302]. https://doi.org/10.3389/fmicb.2017.02302