Molecular mechanism for silencing virally transduced genes involves histone deacetylation and chromatin condensation.
Virally transduced genes are often silenced after integration into the host genome. Chromatin immunoprecipitation and nuclease sensitivity experiments now demonstrate that silencing of the transgene is characterized by deacetylation of histone H4 lysines and chromatin condensation. Trichostatin A treatment results in dramatic reactivation of gene expression that is preceded by histone acetylation and chromatin decondensation. Analysis of individual histone H4 lysines demonstrate that chromatin domain opening is coincident with rapid acetylation of histone H4 K5, K12, and K16 and that maintenance of the open domain is correlated with acetylation of histone H4 K8. Removal of trichostatin A results in rapid deacetylation of histone H4 K8, chromatin condensation, and transcription silencing. The results suggest that deacetylation of histone H4 lysines and coincident chromatin condensation are critically involved in the silencing of virally transduced genes.
Chen
W Y
WY
Department of Biochemistry, School of Medicine and Dentistry, University of Alabama, Birmingham, AL 35294, USA.
Townes
T M
TM
D000107:Acetylation; D000228:Adenine Phosphoribosyltransferase / Q000235:genetics; D002843:Chromatin / Q000378:metabolism*; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D000229:Dependovirus / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D015967:Gene Expression Regulation, Viral / Q000187:drug effects*; D020868:Gene Silencing; D005814:Genes, Viral / Q000235:genetics; D006367:HeLa Cells; D006651:Histocytochemistry; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007763:Lac Operon / Q000235:genetics; D008239:Lysine / Q000378:metabolism; D011233:Precipitin Tests; D014161:Transduction, Genetic / Q000235:genetics*; D019076:Transgenes / Q000235:genetics
D002843:Chromatin; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D000228:Adenine Phosphoribosyltransferase; C032824:ATCGAT-specific type II deoxyribonucleases; D015252:Deoxyribonucleases, Type II Site-Specific; D008239:Lysine