Epigenetic histone modification of Epstein-Barr virus BZLF1 promoter during latency and reactivation in Raji cells

Takayuki Murata, Yutaka Kondo, Atsuko Sugimoto, Daisuke Kawashima, Shinichi Saito, Hiroki Isomura, Teru Kanda, Tatsuya Tsurumi

研究成果: Article査読

65 被引用数 (Scopus)

抄録

The Epstein-Barr virus (EBV) predominantly establishes latent infection in B cells, and the reactivation of the virus from latency is dependent on the expression of the viral BZLF1 protein. The BZLF1 promoter (Zp) normally exhibits only low basal activity but is activated in response to chemical or biological inducers, such as 12-O-tetradecanoylphorbol-13-acetate (TPA), calcium ionophores, or histone deacetylase (HDAC) inhibitors. In some cell lines latently infected with EBV, an HDAC inhibitor alone can induce BZLF1 transcription, while the treatment does not enhance expression in other cell lines, such as B95-8 or Raji cells, suggesting unknown suppressive mechanisms besides histone deacetylation in those cells. Here, we found the epigenetic modification of the BZLF1 promoter in latent Raji cells by histone H3 lysine 27 trimethylation (H3K27me3), H3K9me2/me3, and H4K20me3. Levels of active markers such as histone acetylation and H3K4me3 were low in latent cells but increased upon reactivation. Treatment with 3-deazaneplanocin A (DZNep), an inhibitor of H3K27me3 and H4K20me3, significantly enhanced the BZLF1 transcription in Raji cells when in combination with an HDAC inhibitor, trichostatin A (TSA). The knockdown of Ezh2 or Suv420h1, histone methyltransferases for H3K27me3 or H4K20me3, respectively, further proved the suppression of Zp by the methylations. Taken together, the results indicate that H3K27 methylation and H4K20 methylation are involved, at least partly, in the maintenance of latency, and histone acetylation and H3K4 methylation correlate with the reactivation of the virus in Raji cells.

本文言語English
ページ(範囲)4752-4761
ページ数10
ジャーナルJournal of Virology
86
9
DOI
出版ステータスPublished - 05-2012
外部発表はい

All Science Journal Classification (ASJC) codes

  • 微生物学
  • 免疫学
  • 昆虫科学
  • ウイルス学

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