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Series GSE242448 Query DataSets for GSE242448
Status Public on Nov 29, 2023
Title Ten-eleven translocation (Tet) methylcytosine dioxygenases dependent viral DNA demethylation mediates in vivo hepatitis B virus (HBV) biosynthesis
Organism Hepatitis B virus
Experiment type Methylation profiling by high throughput sequencing
Summary Liver-specific ten-eleven translocation methylcytosine dioxygenases 2 and 3 (Tet2 plus Tet3)-deficient hepatitis B virus (HBV) transgenic mice fail to support viral biosynthesis. The levels of viral transcription and replication intermediates are dramatically reduced. Hepatitis B core antigen (HBcAg) is only observed in a very limited number of pericentral hepatocytes in a pattern that is similar to glutamate-ammonia ligase (Glul), a -catenin target gene. HBV transcript abundance in Tet-deficient mice resembles that observed in wild-type neonatal mice. Furthermore, the RNA levels of several -catenin target genes including Glul, Lhpp, Notun, Oat, Slc1a2 and Tbx3, in Tet-deficient mice was also similar to that observed in wild-type neonatal mice. As HBV transcription is regulated by -catenin, these finding support the suggestion that neonatal Tet-deficiency might limit -catenin target gene expression, limiting viral biosynthesis. Additionally, HBV transgene DNA displays increased 5-methylcytosine (5mC) frequency at CpG sequences consistent with neonatal Tet-deficiency being responsible for decreased developmental viral DNA demethylation mediated by 5mC oxidation to 5-hydroxymethylcytosine (5hmC), a process that might be responsible for the reduction in cellular -catenin target gene expression and viral transcription and replication.
 
Overall design Liver-specific Tet2-delete, Tet3-deleted and Tet2 plus Tet3-deleted HBV transgenic mice were generated and characterized to determine the role for Tet enzymes in the liver-specific demethylation of HBV transgene DNA which is associated with viral biosynthesis in this model of chronic infection.
 
Contributor(s) Matrenec R, Oropeza CE, Dekoven E, Tarnow G, Maienschein-Cline M, Chau CS, Green SJ, McLachlan A
Citation(s) 38179947
Submission date Sep 06, 2023
Last update date Feb 28, 2024
Contact name Mark Maienschein-Cline
E-mail(s) mmaiensc@uic.edu
Organization name University of Illinois at Chicago
Department Research Resources Center
Lab Center for Research Informatics
Street address 1819 W Polk Ave, Rm 336 M/C 789
City Chicago
State/province IL
ZIP/Postal code 60612
Country USA
 
Platforms (1)
GPL33735 Illumina MiSeq (Hepatitis B virus)
Samples (38)
GSM7763624 Control Female.1 [F10]
GSM7763625 Tet2-deficient Female.1 [F11]
GSM7763626 Tet2-deficient Female.2 [F12]
Relations
BioProject PRJNA1013490

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE242448_HBV.fa.gz 1.1 Kb (ftp)(http) FA
GSE242448_methyl_levels.txt.gz 28.8 Kb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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