ArticleClinical epigenetics2016
Increased Set1 binding at the promoter induces aberrant epigenetic alterations and up-regulates cyclic adenosine 5'-monophosphate response element modulator alpha in systemic lupus erythematosus.
Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- The emerging role of histone acetylation in rheumatic diseases: unraveling mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- Methylation of T and B Lymphocytes in Autoimmune Rheumatic Diseases.Clinical reviews in allergy & immunology · 2024Review
- Novel Aspects of cAMP-Response Element Modulator (CREM) Role in Spermatogenesis and Male Fertility.International journal of molecular sciences · 2023Review
- Decreased SUV39H1 at the promoter region leads to increased CREMα and accelerates autoimmune response in CD4Clinical epigenetics · 2022Article
- The Role of Oxidative Stress in Epigenetic Changes Underlying Autoimmunity.Antioxidants & redox signaling · 2022Review
- Comparative Analysis on Abnormal Methylome of Differentially Expressed Genes and Disease Pathways in the Immune Cells of RA and SLE.Frontiers in immunology · 2021Article
- Clinical value of DNA methylation markers in autoimmune rheumatic diseases.Nature reviews. Rheumatology · 2020Review
- DNA methylation changes on immune cells in Systemic Lupus Erythematosus.Autoimmunity · 2020Review
- Aberrant RNA Splicing Events Driven by Mutations of RNA-Binding Proteins as Indicators for Skin Cutaneous Melanoma Prognosis.Frontiers in oncology · 2020Article
- [Effect of aberrant H3K27me3 modification in promoter regions on cAMP response element modulator α expression in CD4Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2017Article
- Epigenetic involvement in etiopathogenesis and implications in treatment of systemic lupus erythematous.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Review
- SLE-Associated Defects Promote Altered T Cell Function.Critical reviews in immunology · 2017Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundUp-regulated cyclic adenosine 5'-monophosphate response element modulator α (CREMα) which can inhibit IL-2 and induce IL-17A in T cells plays a critical role in the pathogenesis of systemic lupus erythematosus (SLE). This research aimed to investigate the mechanisms regulating CREMα expression in SLE.
resultsFrom the chromatin immunoprecipitation (ChIP) microarray data, we found a sharply increased H3 lysine 4 trimethylation (H3K4me3) amount at the CREMα promoter in SLE CD4+ T cells compared to controls. Then, by ChIP and real-time PCR, we confirmed this result. Moreover, H3K4me3 amount at the promoter was positively correlated with CREMα mRNA level in SLE CD4+ T cells. In addition, a striking increase was observed in SET domain containing 1 (Set1) enrichment, but no marked change in mixed-lineage leukemia 1 (MLL1) enrichment at the CREMα promoter in SLE CD4+ T cells. We also proved Set1 enrichment was positively correlated with both H3K4me3 amount at the CREMα promoter and CREMα mRNA level in SLE CD4+ T cells. Knocking down Set1 with siRNA in SLE CD4+ T cells decreased Set1 and H3K4me3 enrichments, and elevated the levels of DNMT3a and DNA methylation, while the amounts of H3 acetylation (H3ac) and H4 acetylation (H4ac) didn't alter greatly at the CREMα promoter. All these changes inhibited the expression of CREMα, then augmented IL-2 and down-modulated IL-17A productions. Subsequently, we observed that DNA methyltransferase (DNMT) 3a enrichment at the CREMα promoter was down-regulated significantly in SLE CD4+ T cells, and H3K4me3 amount was negatively correlated with both DNA methylation level and DNMT3a enrichment at the CREMα promoter in SLE CD4+ T cells.
conclusionsIn SLE CD4+ T cells, increased Set1 enrichment up-regulates H3K4me3 amount at the CREMα promoter, which antagonizes DNMT3a and suppresses DNA methylation within this region. All these factors induce CREMα overexpression, consequently result in IL-2 under-expression and IL-17A overproduction, and contribute to SLE at last. Our findings provide a novel approach in SLE treatment.
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