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| Status |
Public on Aug 13, 2017 |
| Title |
DNA Methylation-dependent regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
Methylation profiling by high throughput sequencing
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| Summary |
Global DNA hypomethylation in CD4+ cells in SLE patients was suggested to play a key role in the pathogenesis. To identify new methylation-sensitive genes, we integrated genome-wide DNA methylation and mRNA profiling in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Ctse, in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was hypomethylated and mutated to CGGG in MRL mice. Kaiso is known to bind mCGCG and we hypothesized that it represses expression of Ctse. The binding of Kaiso to mCGCG site in B6 was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or TSA showed the suppression of the binding of Kaiso to mCGCG motif and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. Accordingly, IL10 and CTSE mRNAs up-regulated in CD4+ T cells both in MRL mice and the patients with SLE. The hypomethylation of mCGCG motif, reduced recruitment of Kaiso, and increased expression of Ctse and Il-10 in CD4+ cells may be involved in the pathogenesis of SLE.
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| Overall design |
To identify new candidate genes regulated by DNA methylation and involved in the pathogenesis of systemic lupus erythematosus (SLE), we performed Illumina Hiseq to analyze the genome-wide DNA methylation and expression of mRNA of CD4+ T cell isolated from spleens in MRL/lpr-Tnfrsf6lpr (MRL) mice and C57BL/6J (B6) mice. Both mice are female, 16 weeks old. For Illumina analysis, we used one mouse of MRL mice and one mouse of B6 mice.
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| Contributor(s) |
Wada J, Hiramatsu S |
| Citation(s) |
30816218 |
| |
| Submission date |
Aug 09, 2017 |
| Last update date |
Jul 25, 2021 |
| Contact name |
Jun Wada |
| E-mail(s) |
[email protected]
|
| Phone |
81862357232
|
| Organization name |
Okayama University
|
| Department |
Department of Nephrology, Rheumatology, Endocrinology and Metabolism
|
| Street address |
2-5-1 Shikata-cho, Kita-ku
|
| City |
Okayama |
| ZIP/Postal code |
7008558 |
| Country |
Japan |
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| Platforms (2) |
| GPL13112 |
Illumina HiSeq 2000 (Mus musculus) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA397745 |
| SRA |
SRP115121 |
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