Regulation of Cathepsin E gene expression by the transcription factor Kaiso in MRL/lpr mice derived CD4+ T cells.
Animals
CD4-Positive T-Lymphocytes
/ immunology
Cathepsin E
/ genetics
Cells, Cultured
CpG Islands
/ genetics
DNA Methylation
/ immunology
Disease Models, Animal
Female
Gene Expression Regulation
/ immunology
Humans
Interleukin-10
/ immunology
Introns
/ genetics
Lupus Erythematosus, Systemic
/ genetics
Mice
Mice, Inbred C57BL
Mice, Inbred MRL lpr
Mutation
Primary Cell Culture
RNA, Small Interfering
/ metabolism
Transcription Factors
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
28 02 2019
28 02 2019
Historique:
received:
26
06
2018
accepted:
20
11
2018
entrez:
1
3
2019
pubmed:
1
3
2019
medline:
22
9
2020
Statut:
epublish
Résumé
Global DNA hypomethylation in CD4+ cells in systemic lupus erythematosus (SLE) 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 data in CD4+ cells of MRL/lpr (MRL) and C57BL6/J (B6) mice. We identified Cathepsin E (Ctse), in which 13 methyl-CpGs within 583 bp region of intron 1 were hypomethylated, and Ctse mRNA upregulated in MRL compared with B6 mice. One of methyl-CpGs, mCGCG was 93.3 ± 2.05% methylated in B6 mice, while 80.0 ± 6.2% methylated and mutated to CGGG in MRL mice. Kaiso is known to bind to mCGCG and we hypothesized that it represses expression of Ctse in B6 mice. The binding of Kaiso to mCGCG site in B6 mice was reduced in MRL mice revealed by ChIP-PCR. EL4 cells treated with 5-azaC and/or Trichostatin A showed the suppression of binding of Kaiso to mCGCG motif by ChIP-PCR and the overexpression of Ctse was demonstrated by qPCR. Ctse gene silencing by siRNA in EL4 cells resulted in reduction of IL-10 secretion. 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.
Identifiants
pubmed: 30816218
doi: 10.1038/s41598-019-38809-y
pii: 10.1038/s41598-019-38809-y
pmc: PMC6395770
doi:
Substances chimiques
IL10 protein, mouse
0
RNA, Small Interfering
0
Transcription Factors
0
Zbtb33 protein, mouse
0
Interleukin-10
130068-27-8
Cathepsin E
EC 3.4.23.34
Ctse protein, mouse
EC 3.4.23.34
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
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