Dynamic histone H3 acetylation and methylation at human cytomegalovirus promoters during replication in fibroblasts

被引:74
作者
Cuevas-Bennett, Christian [1 ]
Shenk, Thomas [1 ]
机构
[1] Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1128/JVI.00946-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human cytomegalovirus DNA is packaged in virions without histones but associates with histones upon reaching the nucleus of an infected cell. Since transcription is modulated by the interplay of histone modifications, we used chromatin immunoprecipitation to detect acetylation and methylation of histone H3 at viral promoters at different times during the viral replication cycle. Histone H3 at immediate-early promoters is acetylated at the start of infection, while it is initially methylated at early and late promoters. Acetylation at immediate-early promoters is dynamic, with a high level of activating modifications at 3 and 6 h postinfection (hpi), followed by a marked reduction at 12 hpi. All viral promoters, as well as nonpromoter regions, are modified with activating acetylations at 24 to 72 hpi. The transient reduction in histone H3 acetylation at the major immediate-early promoter depends on the cis-repressive sequence to which the UL122-coded IE2 protein binds. A mutant virus lacking this element exhibited decreased IE2 binding at the major immediate-early promoter and failed to show reduced acetylation of histone H3 residing at this promoter at 12 hpi. Our results demonstrate that cytomegalovirus chromatin undergoes dynamic, promoter-specific histone modifications early in the infectious cycle, after which the entire chromosome becomes highly acetylated.
引用
收藏
页码:9525 / 9536
页数:12
相关论文
共 67 条
[1]   IDENTIFICATION OF BINDING-SITES FOR THE 86-KILODALTON IE2 PROTEIN OF HUMAN CYTOMEGALOVIRUS WITHIN AN IE2-RESPONSIVE VIRAL EARLY PROMOTER [J].
ARLT, H ;
LANG, D ;
GEBERT, S ;
STAMMINGER, T .
JOURNAL OF VIROLOGY, 1994, 68 (07) :4117-4125
[2]  
Ashkar Ali A., 2002, Current Molecular Medicine (Hilversum), V2, P545, DOI 10.2174/1566524023362159
[3]   Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain [J].
Bannister, AJ ;
Zegerman, P ;
Partridge, JF ;
Miska, EA ;
Thomas, JO ;
Allshire, RC ;
Kouzarides, T .
NATURE, 2001, 410 (6824) :120-124
[4]   Endoplasmic reticulum stress induction of the Grp78/BiP promoter: Activating mechanisms mediated by YY1 and its interactive chromatin modifiers [J].
Baumeister, P ;
Luo, SZ ;
Skarnes, WC ;
Sui, GC ;
Seto, E ;
Shi, Y ;
Lee, AS .
MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (11) :4529-4540
[5]   Neutrality of the canonical NF-κB-dependent pathway for human and murine cytomegalovirus transcription and replication in vitro [J].
Benedict, CA ;
Angulo, A ;
Patterson, G ;
Ha, SW ;
Huang, H ;
Messerle, M ;
Ware, CF ;
Ghazal, P .
JOURNAL OF VIROLOGY, 2004, 78 (02) :741-750
[6]   The human cytomegalovirus 86-kilodalton major immediate-early protein interacts physically and functionally with histone acetyltransferase P/CAF [J].
Bryant, LA ;
Mixon, P ;
Davidson, M ;
Bannister, AJ ;
Kouzarides, T ;
Sinclair, JH .
JOURNAL OF VIROLOGY, 2000, 74 (16) :7230-7237
[7]   A HUMAN CYTOMEGALO-VIRUS EARLY GENE HAS 3 INDUCIBLE PROMOTERS THAT ARE REGULATED DIFFERENTIALLY AT VARIOUS TIMES AFTER INFECTION [J].
CHANG, CP ;
MALONE, CL ;
STINSKI, MF .
JOURNAL OF VIROLOGY, 1989, 63 (01) :281-290
[8]   HUMAN CYTOMEGALOVIRUS IE2 NEGATIVELY REGULATES ALPHA-GENE EXPRESSION VIA A SHORT TARGET SEQUENCE NEAR THE TRANSCRIPTION START SITE [J].
CHERRINGTON, JM ;
KHOURY, EL ;
MOCARSKI, ES .
JOURNAL OF VIROLOGY, 1991, 65 (02) :887-896
[9]   HISTONE MODIFICATIONS IN THE YEAST S-CEREVISIAE [J].
DAVIE, JR ;
SAUNDERS, CA ;
WALSH, JM ;
WEBER, SC .
NUCLEIC ACIDS RESEARCH, 1981, 9 (13) :3205-3216
[10]   Emerging connections between DNA methylation and histone acetylation [J].
Dobosy, JR ;
Selker, EU .
CELLULAR AND MOLECULAR LIFE SCIENCES, 2001, 58 (5-6) :721-727