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| Status |
Public on Dec 10, 2020 |
| Title |
Relative DNA methylation and demethylation efficiencies during postnatal liver development regulate hepatitis B virus biosynthesis |
| Organisms |
Mus musculus; Hepatitis B virus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
HBV transcription and replication increases progressively throughout postnatal liver development with maximal viral biosynthesis occurring at around four weeks of age in the HBV transgenic mouse model of chronic infection. Increasing viral biosynthesis is associated with a corresponding progressive loss of DNA methylation. The loss of DNA methylation is associated with increasing levels of 5-hydroxymethylcytosine (5hmC) residues which correlates with increased liver-enriched pioneer transcription factor Forkhead box protein A (FoxA) RNA levels, a rapid decline in postnatal liver DNA methyltransferase (Dnmt) transcripts and a very modest reduction in Ten-eleven translocation (Tet) methylcytosine dioxygenase expression. These observations are consistent with the suggestion that the balance between active HBV DNA methylation and demethylation is regulated by FoxA recruitment of Tet in the presence of declining Dnmt activity. These changes lead to demethylation of the viral genome during hepatocyte maturation with associated increases in viral biosynthesis. Consequently, manipulation of the relative activities of these two counter-balancing processes might permit the specific silencing of HBV gene expression with the loss of viral biosynthesis and the resolution of chronic HBV infections.
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| Overall design |
Bisulfite and oxidative bisulfite sequencing by amplicon. 58 total samples analyzed in 120 separate libraries. Some bisulfite libraries were prepared in conjunction with oxidative bisulfite libraries and constitute paired samples – these are labeled as "OxBS + BS" in the library protocol. Others were only processed for bisulfite and are labeled "BS only". Amplicons were processed for different regions of the HBV genome, as well as several mouse promoters. Not all samples covered the same total set of amplicons; CpGs with 0 coverage in the processed data file indicate regions that were not covered in a particular file.
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| Contributor(s) |
Oropeza CE, Tarnow G, Taha TY, Shalaby RE, Hyde MV, Maienschein-Cline M, Green SJ, McLachlan A |
| Citation(s) |
33361417 |
| Submission date |
Sep 03, 2020 |
| Last update date |
Mar 11, 2021 |
| Contact name |
Mark Maienschein-Cline |
| E-mail(s) |
mmaiensc@uic.edu
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| Organization name |
University of Illinois at Chicago
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| Department |
Research Resources Center
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| Lab |
Center for Research Informatics
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| Street address |
1819 W Polk Ave, Rm 336 M/C 789
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60612 |
| Country |
USA |
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| Platforms (1) |
| GPL29102 |
Illumina MiSeq (Hepatitis B virus; Mus musculus) |
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| Samples (120)
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| Relations |
| BioProject |
PRJNA661325 |
| SRA |
SRP280021 |
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