Control of cytomegalovirus lytic gene expression by histone acetylation

被引:180
作者
Murphy, JC [1 ]
Fischle, W
Verdin, E
Sinclair, JH
机构
[1] Univ Cambridge, Dept Med, Cambridge CB2 2QQ, England
[2] Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA
基金
英国医学研究理事会;
关键词
cytomegalovirus; heterochromatin protein 1; histone acetylation; immediate early; latency;
D O I
10.1093/emboj/21.5.1112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 H-DACs 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 MEEP activity. We further show that the MIEP associates with acetylated histories 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.
引用
收藏
页码:1112 / 1120
页数:9
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