دورية أكاديمية
A targeted RNA interference screen reveals novel epigenetic factors that regulate herpesviral gene expression.
العنوان: | A targeted RNA interference screen reveals novel epigenetic factors that regulate herpesviral gene expression. |
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المؤلفون: | Oh HS, Bryant KF, Nieland TJ, Mazumder A, Bagul M, Bathe M, Root DE, Knipe DM |
المصدر: | MBio [mBio] 2014 Feb 04; Vol. 5 (1), pp. e01086-13. Date of Electronic Publication: 2014 Feb 04. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
مواضيع طبية MeSH: | Epigenesis, Genetic* , Gene Expression Regulation, Viral* , Host-Pathogen Interactions*, Genetic Testing/*methods , Simplexvirus/*genetics, Cell Line, Tumor ; Humans ; RNA Interference ; Simplexvirus/physiology |
مستخلص: | Unlabelled: Herpes simplex virus (HSV) utilizes and subverts host chromatin mechanisms to express its lytic gene products in mammalian cells. The host cell attempts to silence the incoming viral genome by epigenetic mechanisms, but the viral VP16 and ICP0 proteins promote active chromatin on the viral genome by recruiting other host epigenetic factors. However, the dependence on VP16 and ICP0 differs in different cell lines, implying cell type-dependent functional contributions of epigenetic factors for HSV gene expression. In this study, we performed a targeted RNA interference (RNAi) screen for cellular chromatin factors that are involved in regulation of herpes simplex virus (HSV) gene expression in U2OS osteosarcoma cells, a cell line that complements ICP0 mutant and VP16 mutant virus replication. In this screen, we found the same general classes of chromatin factors that regulate HSV gene expression in U2OS cells as in other cell types, including histone demethylases (HDMs), histone deacetylases (HDACs), histone acetyltransferases (HATs), and chromatin-remodeling factors, but the specific factors within these classes are different from those identified previously for other cell types. For example, KDM3A and KDM1A (LSD1) both demethylate mono- and dimethylated H3K9, but KDM3A emerged in our screen of U2OS cells. Further, small interfering RNA (siRNA) and inhibitor studies support the idea that KDM1A is more critical in HeLa cells, as observed previously, while KDM3A is more critical in U2OS cells. These results argue that different cellular chromatin factors are critical in different cell lines to carry out the positive and negative epigenetic effects exerted on the HSV genome. Importance: Upon entry into the host cell nucleus, the herpes simplex virus genome is subjected to host epigenetic silencing mechanisms. Viral proteins recruit cellular epigenetic activator proteins to reverse and counter the cellular silencing mechanisms. Some of the host silencing and activator functions involved in HSV gene expression have been identified, but there have been indications that the host cell factors may vary in different cell types. In this study, we performed a screen of chromatin factors involved in HSV gene regulation in osteosarcoma cells, and we found that the chromatin factors that are critical for HSV gene expression in these cells are different from those for previously studied cell types. These results argue that the specific chromatin factors operative in different cell lines and cell types may differ. This has implications for epigenetic drugs that are under development. |
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معلومات مُعتمدة: | P30 ES002109 United States ES NIEHS NIH HHS; R01 AI063106 United States AI NIAID NIH HHS; P30-ES002109 United States ES NIEHS NIH HHS; AI063106 United States AI NIAID NIH HHS |
تواريخ الأحداث: | Date Created: 20140206 Date Completed: 20140826 Latest Revision: 20211021 |
رمز التحديث: | 20231215 |
مُعرف محوري في PubMed: | PMC3950524 |
DOI: | 10.1128/mBio.01086-13 |
PMID: | 24496796 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2150-7511 |
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DOI: | 10.1128/mBio.01086-13 |