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RISS 인기검색어
- 검색키워드
- 저자 : Paul M. Lieberman (검색결과 3 건)
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Kang, Hyojeung,Cho, Hyosun,Sung, Gi-Ho,Lieberman, Paul M. American Society for Microbiology 2013 Journal of virology Vol.87 No.3
<B>ABSTRACT</B><P>CCCTC-binding factor (CTCF) has been implicated in various aspects of viral and host chromatin organization and transcriptional control. We showed previously that CTCF binds to a cluster of three sites in the first intron of the Kaposi's sarcoma-associated herpesvirus (KSHV) multicistronic latency-associated transcript that encodes latency-associated nuclear antigen (LANA), viral cyclin (vCyclin), vFLIP, viral microRNAs, and kaposin. We show here that these CTCF binding sites regulate mRNA production, RNA polymerase II (RNAPII) programming, and nucleosome organization of the KSHV latency transcript control region. We also show that KSHV bacmids lacking these CTCF binding sites have elevated and altered ratios of spliced latency transcripts. CTCF binding site mutations altered RNAPII and RNAPII-accessory factor interactions with the latency control region. CTCF binding sites were required for the<I>in vitro</I>recruitment of RNAPII to the latency control region, suggesting that direct interactions between CTCF and RNAPII contribute to transcription regulation. Histone modifications in the latency control region were also altered by mutations in the CTCF binding sites. Finally, we show that CTCF binding alters the regular phasing of nucleosomes in the latency gene transcript and intron, suggesting that nucleosome positioning can be an underlying biochemical mechanism of CTCF function. We propose that RNAPII interactions and nucleosome displacement serve as a biochemical basis for programming RNAPII in the KSHV transcriptional control region.</P>
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최수진,신유수,강병욱,김종광,원경재,Paul M. Lieberman,조효선,강효정 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.8
Epstein-Barr virus (EBV)-associated gastriccarcinoma (EBVaGC) is a recently recognized diseaseentity defined by the presence of EBV in gastric carcinomacells. EBV infection causes major epigenetic alterations inthe EBV genome and its cellular host genome, suggestingthat EBV acts as a direct epigenetic driver for EBVaGC. One of the major epigenetic events in the viral and cellulargenomes to control transcription is DNA hypo- or hypermethylation. Particularly, local and global hypermethylationhave been reported in EBVaGC. It is thereforeimportant to understand the molecular mechanisms ofDNA hypermethylation during EBVaGC carcinogenesis. To understand the functional roles of DNA methylationand suggest therapeutic target candidates for EBVaGC, wereviewed recent literature reporting DNA hypermethylationin EBVaGC. We summarized the identified candidategenes that are markedly hypermethylated in EBVaGC,which can potentially be targets for chemotherapies withdemethylating agents.
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Bioactive Activities of Natural Products against Herpesvirus Infection
손명기,이민정,성기호,이태호,Yu Su Shin,Hyosun Cho,Paul M. Lieberman,강효정 한국미생물학회 2013 The journal of microbiology Vol.51 No.5
More than 90% of adults have been infected with at least one human herpesvirus, which establish long-term latent infection for the life of the host. While anti-viral drugs exist that limit herpesvirus replication, many of these are ineffective against latent infection. Moreover, drug-resistant strains of herpesvirus emerge following chemotherapeutic treatment. For example, resistance to acyclovir and related nucleoside analogues can occur when mutations arise in either HSV thymidine kinase or DNA polymerases. Thus, there exists an unmet medical need to develop new anti-herpesvirus agents with different mechanisms of action. In this Review, we discuss the promise of anti-herpetic substances derived from natural products including extracts and pure compounds from potential herbal medicines. One example is Glycyrrhizic acid isolated from licorice that shows promising antiviral activity towards human gammaherpesviruses. Secondly, we discuss anti-herpetic mechanisms utilized by several natural products in molecular level. While nucleoside analogues inhibit replicating herpesviruses in lytic replication, some natural products can disrupt the herpesvirus latent infection in the host cell. In addition, natural products can stimulate immune responses against herpesviral infection. These findings suggest that natural products could be one of the best choices for development of new treatments for latent herpesvirus infection, and may provide synergistic anti-viral activity when supplemented with nucleoside analogues. Therefore, it is important to identify which natural products are more efficacious anti-herpetic agents, and to understand the molecular mechanism in detail for further advance in the anti-viral therapies.
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