Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells

Yongwei Lai; Zhao He; Aowei Zhang; Zhinan Yan; Xiao Zhang; Shiyue Hu; Nan Wang; Hongpeng He

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자료유형: 학술저널

저자정보: Yongwei Lai (Tianjin University of Science and Technology) Zhao He (Tianjin University of Science and Technology) Aowei Zhang (Tianjin University of Science and Technology) Zhinan Yan (Tianjin University of Science and Technology) Xiao Zhang (Tianjin University of Science and Technology) Shiyue Hu (Tianjin University of Science and Technology) Nan Wang (Tianjin University of Science and Technology) Hongpeng He (Tianjin University of Science and Technology)

저널정보: 한국유전학회 Genes & Genomics Genes & Genomics Vol.42 No.6

발행연도: 2020.1

수록면: 691 - 698 (8page)

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Background High-risk HPV is a causative factor of cervical cancer. HPV DNA fragments integrate into host genome resulting in the constitutive expression of HPV genes E6 and E7 under the regulation of transcription factors, such as p300 and Tip60. Interestingly, Tip60, a factor with HAT (histone acetyl transferase) activity, represses HPV18 E6/E7 genes while another HAT p300 activates the transcription of HPV18 E6/E7. Objective To explore the mechanism for the opposite roles of Tip60 and p300 in the virus gene regulation, and the influence of Tip60 and p300 in histone modifications in the regulatory sequence of HPV18 genes. Methods Tip60 or p300 was either knocked down or overexpressed in HeLa cells. The effects on HPV E6E7 expression were determined with RT-qPCR. The association of RNA polymerase II and the enrichment of acetylated or methylated histones in HPV promoter region were measured by ChIP assays with specific antibodies. Results ChIP results showed that Tip60 and p300 differently affected the modifications of histone H3K9 and the deposition of nucleosomes in HPV18 long control region (LCR). HPV18 LCR in HeLa cells is bivalent chromatin carrying both the active histone H3K9 acetylation mark and the repressive histone H3K9 trimethylation mark, the balance is maintained by Tip60 and p300. Conclusion(s) Based on the roles of Tip60 and p300 in HPV gene regulation, chemical compounds targeting Tip60 or p300 are potential anti-cervical cancer drugs.

#HPV18 E6/E7 · Transcriptional regulation · Tip60 · p300 · Histone modification

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