TITLE

Methylation Regulates Hepatitis B Viral Protein Expression

AUTHOR(S)
Vivekanandan, Perumal; Thomas, David; Torbenson, Michael
PUB. DATE
May 2009
SOURCE
Journal of Infectious Diseases;5/1/2009, Vol. 199 Issue 9, p1286
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background. Hepatitis B virus (HBV)DNAhas been shown to contain CpG islands that are methylated in human tissue, which suggests a role for methylation in regulating viral protein production. However, data are lacking about whether methylation regulates viral gene expression. Methods. To investigate the hypothesis that methylation of viral DNA regulates viral gene expression, unmethylated, partially methylated, and fully methylated viralDNAwas transfected into HepG2 cells. In addition, a new assay was designed that specifically identifies methylated covalently closed circular DNA (cccDNA) in human liver tissue. Results. Transfection of methylated HBV DNA led to reduced HBV mRNA levels in HepG2 cells, decreased surface and core protein expression in these cells, and decreased secretion of HBV viral proteins into the cell supernatant. These data provide direct evidence that CpG islands regulate gene transcription of HBV. Furthermore, methylated cccDNA was found in tumor and nonneoplastic human liver tissues. Finally, an in vitro equivalent of cccDNA showed decreased viral protein production in HepG2 cells after DNA methylation. Conclusion. Taken together, these data demonstrate that methylation of viral CpG islands can regulate viral protein production.
ACCESSION #
39795310

 

Related Articles

  • Seladin-1 expression is regulated by promoter methylation in adrenal cancer. Simi, Lisa; Malentacchi, Francesca; Luciani, Paola; Gelmini, Stefania; Deledda, Cristiana; Arvia, Rosaria; Mannelli, Massimo; Peri, Alessandro; Orlando, Claudio // BMC Cancer;2010, Vol. 10, p201 

    Background: Seladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now...

  • Validation of miRNA-mRNA interactions by electrophoretic mobility shift assays. Solé, Anna; Mencia, Núria; Villalobos, Xenia; Noé, Véronique; Ciudad, Carlos J. // BMC Research Notes;2013, Vol. 6 Issue 1, p1 

    Background MicroRNAs are small non-coding RNAs involved in gene expression regulation by targeting specific regions in the 3'-UTR of the mRNA of their target genes. This binding leads to a decrease in the protein levels of such genes either by mRNA degradation or mRNA destabilization and...

  • High Guanine and Cytosine Content Increases mRNA Levels in Mammalian Cells. Kudla, Grzegorz; Lipinski, Leszek; Caffin, Fanny; Helwak, Aleksandra; Zylicz, Maciej // PLoS Biology;Jun2006, Vol. 4 Issue 6, pe180 

    Mammalian genes are highly heterogeneous with respect to their nucleotide composition, but the functional consequences of this heterogeneity are not clear. In the previous studies, weak positive or negative correlations have been found between the silent-site guanine and cytosine (GC) content...

  • Endogenous microRNA regulation suppresses transgene expression in hematopoietic lineages and enables stable gene transfer. Brown, Brian D.; Venneri, Mary Anna; Zingale, Anna; Sergi, Lucia Sergi; Naldini, Luigi // Nature Medicine;May2006, Vol. 12 Issue 5, p585 

    MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression by repressing translation of target cellular transcripts. Increasing evidence indicates that miRNAs have distinct expression profiles and play crucial roles in numerous cellular processes, although the extent of miRNA...

  • Hepatitis B virus X protein upregulates DNA methyltransferase 3A/3B and enhances SOCS-1CpG island methylation. XIAOYU FU; XIAOLING SONG; YANYAN LI; DEMING TAN; GUOZHEN LIU // Molecular Medicine Reports;2016, Vol. 13 Issue 1, p301 

    The aim of the present study was to investigate the effect of hepatitis B virus X protein (HBx) on the expression of DNA methyltransferase (DNMT)3A/3B and suppressors of cytokine signaling-1 (SOCS-1), as well as promoter CpG island methylation of the SOCS-1 gene. Stable hepatocyte cell lines...

  • An expressed pseudogene regulates the messenger-RNA stability of its homologous coding gene. Hirotsune, Shinji; Yoshida, Noriyuki; Chen, Amy; Garrett, Lisa; Sugiyama, Fumihiro; Takahashi, Satoru; Yagami, Ken-ichi; Wynshaw-Boris, Anthony; Yoshiki, Atsushi // Nature;5/1/2003, Vol. 423 Issue 6935, p91 

    A pseudogene is a gene copy that does not produce a functional, full-length protein. The human genome is estimated to contain up to 20,000 pseudogenes. Although much effort has been devoted to understanding the function of pseudogenes, their biological roles remain largely unknown. Here we...

  • MicroRNA-mediated regulation of target genes in several brain regions is correlated to both microRNA-targeting-specific promoter methylation and differential microRNA expression. Taguchi, Y.-h. // BioData Mining;2013, Vol. 6 Issue 1, p1 

    Background: Public domain databases nowadays provide multiple layers of genome-wide data e.g., promoter methylation, mRNA expression, and miRNA expression and should enable integrative modeling of the mechanisms of regulation of gene expression. However, researches along this line were not...

  • Regulation of MLH1 mRNA and protein expression by promoter methylation in primary colorectal cancer: a descriptive and prognostic cancer marker study. Jensen, Lars; Rasmussen, Anders; Byriel, Lene; Kuramochi, Hidekazu; Crüger, Dorthe; Lindebjerg, Jan; Danenberg, Peter; Jakobsen, Anders; Danenberg, Kathleen // Cellular Oncology (2211-3428);Oct2013, Vol. 36 Issue 5, p411 

    Background: In colorectal cancer MLH1 deficiency causes microsatellite instability, which is relevant for the patient's prognosis and treatment, and its putative heredity. Dysfunction of MLH1 is caused by sporadic gene promoter hypermethylation or by hereditary mutations as seen in Lynch...

  • microRNA-Mediated Messenger RNA Deadenylation Contributes to Translational Repression in Mammalian Cells. Beilharz, Traude H.; Humphreys, David T.; Clancy, Jennifer L.; Thermann, Rolf; Martin, David I. K.; Hentze, Matthias W.; Preiss, Thomas // PLoS ONE;2009, Vol. 4 Issue 8, p1 

    Animal microRNAs (miRNAs) typically regulate gene expression by binding to partially complementary target sites in the 3' untranslated region (UTR) of messenger RNA (mRNA) reducing its translation and stability. They also commonly induce shortening of the mRNA 3' poly(A) tail, which contributes...

Share

Read the Article

Courtesy of VIRGINIA BEACH PUBLIC LIBRARY AND SYSTEM

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics