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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Dec 04, 2023 |
| Title |
Egr2 deletion in autoimmune-prone C57BL6/lpr mice suppresses the expression of methylation-sensitive Dlk1-Dio3 cluster microRNAs |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Our previous study demonstrated a significant upregulation of a large set of miRNAs at the genomic imprinted Dlk1-Dio3 locus in lymphocytes of diverse murine lupus-prone strains. The upregulation of Dlk1-Dio3 miRNAs in lupus-prone mice is correlated with the global DNA hypomethylation. In this study, by performing genome-wide DNA methylation analysis, we reported that Dlk1-Dio3 genomic region in CD4+ T cells of MRL/lpr mice was hypomethylated, further linking hypomethylation to the increased expression of Dlk1-Dio3 miRNAs in lupus. Then, we assessed the gene expression levels of enzymes that either write (DNA methyltransferases, DNMTs) or erase DNA methylation (Ten-eleven translation proteins, TETs) to understand the molecular contributor to the DNA hypomethylation in MRL/lpr CD4+ T cells. The expression levels of Dnmt1, Dnmt3b, Tet1, and Tet2 were significantly increased in CD4+ T cells of MRL/lpr mice, as well as in B6/lpr and B6.sle123 mice, compared to their respective control mice. These data indicate the significant involvement of the TETs-mediated active demethylation pathway rather than reduced DNMTs-mediated passive demethylation pathway in the hypomethylation of murine lupus CD4+ T cells. The transcription factor, early growth response 2 (EGR2) is critically involved in regulating T cell functions and autoimmunity. In this research, we found that Egr2 deletion in B6/lpr mice notably reduced methylation-sensitive Dlk1-Dio3 cluster miRNAs expression in CD4+ T cells. Surprisingly, even though EGR2 has been shown to induce DNA demethylation by recruiting TET2, we found that deleting Egr2 in B6/lpr mice induced a higher number of hypomethylated DMRs than hypermethylated DMRs at either whole genome or the Dlk1-Dio3 locus in CD4+ T cells of B6/lpr mice. These data are the first finding on the positive role of EGR2 on the expression of Dlk1-Dio3 cluster miRNAs in lupus mice. Given that Dlk1-Dio3 miRNAs target the major signaling pathways in autoimmunity, these data provide a new perspective in understanding the potential pathogenic role of upregulated EGR2 in lupus.
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| Overall design |
Evaluate the methylation difference between CD4+ T cells of MRL/lpr and MRL mice as well as between EGR2-/-B6/lpr and EGR2 fl/fl B6/lpr mice
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| Contributor(s) |
Dai R, Ahmed SA, Wang Z |
| Citation(s) |
38153351 |
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| Submission date |
Sep 12, 2023 |
| Last update date |
Jan 16, 2024 |
| Contact name |
Zhuang Wang |
| E-mail(s) |
[email protected]
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| Phone |
5303027590
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| Organization name |
VIRGINIA POLYTECHNIC INSTITUTE AND STATE UNIVERSITY
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| Street address |
1739 Autumn Splendor Way
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| City |
Blacksburg |
| State/province |
VA |
| ZIP/Postal code |
24060-2584 |
| Country |
USA |
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| Platforms (2) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (10)
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| Relations |
| BioProject |
PRJNA1015618 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE242955_EGR2_annotated_DMR.xlsx |
780.4 Kb |
(ftp)(http) |
XLSX |
| GSE242955_EGR2_annotated_DMS.xlsx |
4.1 Mb |
(ftp)(http) |
XLSX |
| GSE242955_MRLvsMRL-lpr_DMR_anno.xlsx |
543.9 Kb |
(ftp)(http) |
XLSX |
| GSE242955_MRLvsMRL-lpr_DMS_anno.xlsx |
102.2 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
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