Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MiRNAs expression in the splenic CD4+ T cells and B cells isolated from MRL/lpr mice at 5 and 16 weeks of age

ABSTRACT: To identify any differentially expressed miRNAs in the CD4+ T cells of lupus. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including human lupus. By using high-throughput microRNA profiling analysis, we identified that two miRNAs (miR-21 and miR-148a) overexpressed in CD4+ T cells from both lupus patients and lupus-prone MRL/lpr mice,which promote cell hypomethylation by repressing DNA methyltransferase 1 (DNMT1) expression. We isolated the splenic CD4+ T cells and B cells from MRL/lpr mice at 5 and 16 weeks of age.Cells were collected and total RNA was extracted for the TaqMan® Low Density Assay v2.0 Normalization was performed with snoRNA202, reference snRNAs for mouse.Comparative real-time PCR was performed in triplicate, including no-template.controls. Relative expression was calculated with the comparative cycle threshold method.

ORGANISM(S): Mus musculus

SUBMITTER: Nan Shen

PROVIDER: E-GEOD-21220 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1.

Pan Wen W Zhu Shu S Yuan Min M Cui Huijuan H Wang Lijia L Luo Xiaobing X Li Jia J Zhou Haibo H Tang Yuanjia Y Shen Nan N

Journal of immunology (Baltimore, Md. : 1950) 20100517 12

Systemic lupus erythematosus is a complex autoimmune disease caused by genetic and epigenetic alterations. DNA methylation abnormalities play an important role in systemic lupus erythematosus disease processes. MicroRNAs (miRNAs) have been implicated as fine-tuning regulators controlling diverse biological processes at the level of posttranscriptional repression. Dysregulation of miRNAs has been described in various disease states, including human lupus. Whereas previous studies have shown miRNA ...[more]

PMID: 20483747

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Project description: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.

Dataset Information

MiRNAs expression in the splenic CD4+ T cells and B cells isolated from MRL/lpr mice at 5 and 16 weeks of age

Publications

MicroRNA-21 and microRNA-148a contribute to DNA hypomethylation in lupus CD4+ T cells by directly and indirectly targeting DNA methyltransferase 1.

Similar Datasets

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