Control of cytomegalovirus lytic gene expression by histone acetylation

Jane C. Murphy, Wolfgang Fischle, Eric Verdin, John H. Sinclair

Research output: Contribution to journalArticlepeer-review

173 Scopus citations

Abstract

Permissiveness for human cytomegalovirus (HCMV) infection is dependent on the state of cellular differentiation and has been linked to repression of the viral major immediate early promoter (MIEP). We have used conditionally permissive cells to analyze differential regulation of the MIEP and possible mechanisms involved in latency. Our data suggest that histone deacetylases (HDACs) are involved in repression of the MIEP in non-permissive cells as inhibition of HDACs induces viral permissiveness and increases MIEP activity. Non-permissive cells contain the class I HDAC, HDAC3; super-expression of HDAC3 in normally permissive cells reduces infection and MIEP activity. We further show that the MIEP associates with acetylated histones in permissive cells, and that in peripheral blood monocytes the MIEP associates with heterochromatin protein 1 (HP1), a chromosomal protein implicated in gene silencing. As monocytes are believed to be a site of viral latency in HCMV carriers and reactivated virus is only observed upon differentiation into macrophages, we propose that chromatin remodeling of the MIEP following cellular differentiation could potentially play a role in reactivation of latent HCMV.

Original languageEnglish (US)
Pages (from-to)1112-1120
Number of pages9
JournalEMBO Journal
Volume21
Issue number5
DOIs
StatePublished - Mar 1 2002

Keywords

  • Cytomegalovirus
  • Heterochromatin protein 1
  • Histone acetylation
  • Immediate early
  • Latency

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Control of cytomegalovirus lytic gene expression by histone acetylation'. Together they form a unique fingerprint.

Cite this