TY - JOUR
T1 - Characterization of a suppressive Cis-acting element in the Epstein-Barr virus LMP1 promoter
AU - Yoshida, Masahiro
AU - Murata, Takayuki
AU - Ashio, Keiji
AU - Narita, Yohei
AU - Watanabe, Takahiro
AU - Al Masud, H. M.Abdullah
AU - Sato, Yoshitaka
AU - Goshima, Fumi
AU - Kimura, Hiroshi
N1 - Funding Information:
We thank Drs. W. Hammerschmidt and H. J. Delecluse, T. Tsurumi and T. Kanda for materials and discussions. This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology [to TM (15K08494), to HK (17H04081), to YS (16H06231), and YN (14J01982)], and the Japan Agency for Medical Research and Development [to TM (Japanese Initiative for Progress of Research on Infectious Disease for Global Epidemic, 17fm0208016) and to HK (Practical Research Project for Rare/Intractable Diseases, 15ek0109098)], and partly by the Takeda Science Foundation (to TM).
Publisher Copyright:
© 2017 Yoshida, Murata, Ashio, Narita, Watanabe, Masud, Sato, Goshima and Kimura.
PY - 2017/11/22
Y1 - 2017/11/22
N2 - 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.
AB - 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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U2 - 10.3389/fmicb.2017.02302
DO - 10.3389/fmicb.2017.02302
M3 - Article
AN - SCOPUS:85034653087
VL - 8
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
IS - NOV
M1 - 2302
ER -