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Human papillomavirus E7 oncoprotein induces KDM6A and KDM6B histone demethylase expression and causes epigenetic reprogramming
Abstract
Despite the availability of vaccines, human papillomavirus (HPV) infections remain a cause of significant cancer morbidity and mortality. We have previously shown that HPV16 E7 associates with and diminishes E2F6-containing polycomb repressive complexes. Here, we show that repressive trimethyl marks on lysine 27 of histone 3, which are necessary for binding of polycomb repressive complexes, are decreased in HPV16 E7-expressing cells and HPV16-positive cervical lesions. This is caused by transcriptional induction of the KDM6A and KDM6B histone 3 lysine 27-specific demethylases. HPV16 E7-mediated KDM6B induction accounts for expression of the cervical cancer biomarker, p16 INK4A . Moreover, KDM6A- and KDM6B-responsive Homeobox genes are expressed at significantly higher levels, suggesting that HPV16 E7 results in reprogramming of host epithelial cells. These effects are independent of the ability of E7 to inhibit the retinoblastoma tumor suppressor protein. Most importantly, these effects are reversed when E7 expression is silenced, indicating that this pathway may have prognostic and/or therapeutic significance.
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“KDM6A- and KDM6B-responsive Homeobox (HOX) genes are expressed at significantly higher levels, suggesting that ectopic expression of HPV-16 E7 results in reprogramming of host epithelial cells [331]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [331]
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“HPV E7 has also been shown to induce expression of histone H3 lysine 27 demethylase, KDM6A and KDM6B, enzymes responsible for H3K27me3 demethylation [331]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [331]
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Cited by
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Metadata
- Authors
- McLaughlin-Drubin, M. E., Crum, C. P., & Münger, K.
- Affiliations
- Infectious Diseases Division, Department of Medicine, The Channing Laboratory, Harvard Medical School, Boston, MA 02115; and
- Division of Women's and Perinatal Pathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-01-18
- Volume
- 108
- Issue
- 5
- Pages
- 2130-2135
- ISSN
- 0027-8424
- 1091-6490
- Cited by
- 288
- References
- 9
- Language
- en
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