Human papillomavirus type 16 E7 protein increases acetylation of histone H3 in human foreskin keratinocytes

Benyue Zhang, R. Nicholas Laribee, Michael J. Klemsz, Ann Roman

Research output: Contribution to journalArticlepeer-review

30 Scopus citations

Abstract

Histone acetylation plays an important role in chromatin remodeling and transcription control. Acetylation of histones is regulated by histone acetyltransferases and histone deacetylases (HDACs). Human papillomavirus type 16 (HPV16) E7 can inactivate retinoblastoma protein (pRB), which recruits histone deacetylases, and also physically interacts with histone acetyltransferases and histone deacetylases, suggesting E7 may affect histone acetylation. To test this, we have analyzed the state of acetylation of histone H3 in human foreskin keratinocytes. HPV16 E7 increased acetylation of histone H3 on lysine 9, which is related to transcription activation. The ability to bind both pRB and histone deacetylase was required for HPV16 E7 to increase histone acetylation. Chromatin immunoprecipitations showed HPV16 E7 increases histone acetylation on the E2F1 and cdc25A promoters. Consistent with this, RT-PCR analysis showed an increase in the expression of E2F-responsive genes involved in cell cycle control. HPV16 E7 affected neither the steady-state levels of histone acetyltransferases or deacetylases nor histone deacetylase activity. However, HPV16 E7 did increase the level of methylation of histone H3 on lysine 4, which normally requires displacement of histone deacetylase. In contrast, sodium butyrate, a known inhibitor of histone deacetylases, caused an increase in acetylated but not methylated histone H3. These data suggest HPV16 E7, by increasing histone acetylation, may create a transcriptionally active chromatin structure to promote expression of genes vital for cell cycle progression.

Original languageEnglish (US)
Pages (from-to)189-198
Number of pages10
JournalVirology
Volume329
Issue number1
DOIs
StatePublished - Nov 10 2004

Keywords

  • Histone H3
  • Human foreskin keratinocytes
  • Human papillomavirus type 16 E7 protein

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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