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| Status |
Public on Jan 19, 2018 |
| Title |
Base-resolution analysis of DNA methylation patterns downstream of Dnmt3a in mouse naïve B cells |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Background: The DNA methyltransferase, Dnmt3a, is one of the most commonly mutated genes in adult hematologic malignancies and is dynamically regulated throughout normal B cell development and upon activation by antigenic stimulation. Dnmt3a inactivation in hematopoietic stem cells has been shown to drive B cell-related malignancies, including chronic lymphocytic leukemia, and associates with specific DNA methylation patterns in transformed cells. While a cell-type specific role for Dnmt3a has been proposed in carcinogenesis, the role of Dnmt3a in directing specific DNA methylation patterns in B cell development has not been characterized.
Results: We selectively inactivated Dnmt3a early in B cell development and then utilized Whole Genome Bisulfite Sequencing to generate base-resolution profiles of Dnmt3a+/+ and Dnmt3a−/− mouse naïve splenic B cells. Although overall methylation level distribution was largely consistent between Dnmt3a+/+ and Dnmt3a−/− B cells, we identified site-specific and regional differences corresponding to both gains and losses of methylation in Dnmt3a−/− cells relative to Dnmt3a+/+ cells. Hypomethylated regions (N = 313) in Dnmt3a−/− cells, however, were more frequently observed than were hypermethylated regions (N = 136) by over 2-fold, consistent with loss of methyltransferase activity.
Conclusions: We have identified a set of CpG sites that require Dnmt3a to maintain normal methylation levels in naïve B cells. These CpGs are associated with genes expressed in B cells that undergo dysregulation in leukemias.
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| Overall design |
Base-resolution methylomes for splenic naïve B cells from adult Dnmt3a+/+ and Dnmt3a−/− mice using Whole Genome Bisulfite Sequencing
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| Contributor(s) |
Wade PA |
| Citation(s) |
29326230 |
| |
| Submission date |
Jun 20, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Paul A Wade |
| E-mail(s) |
wadep2@niehs.nih.gov
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| Phone |
919-541-3392
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| Organization name |
NIEHS
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| Department |
Laboratory of Molecular Carcinogenesis
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| Street address |
111 TW Alexander Drive
|
| City |
Research Triangle Park |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA391196 |
| SRA |
SRP109867 |
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