Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts
- PMID: 29465369
Altered gene expression profiles of histone lysine methyltransferases and demethylases in rheumatoid arthritis synovial fibroblasts
Abstract
Objectives: Aberrant histone lysine methylation (HKM) has been reported in rheumatoid arthritis (RA) synovial fibroblasts (SFs). As histone lysine methyltransferases (HKMTs) and demethylases (HKDMs) regulate HKM, these enzymes are believed to be dysregulated in RASFs. The aim of this study is to clarify whether gene expressions of HKMTs and HKDMs are altered in RASFs.
Methods: SFs were isolated from synovial tissues obtained from RA or osteoarthritis (OA) patients during total knee joint replacement. The mRNA levels of 34 HKMTs and 22 HKDMs were examined after stimulation with tumour necrosis factor α (TNF-α) in RASFs and OASFs.
Results: The gene expression of the 12 HKMTs, including MLL1, MLL3, SUV39H1, SUV39H2, PRDM2, EZH2, SETD2, NSD2, NSD3, SMYD4, DOT1, and PR-set7, that catalyse the methylation of H3K4, H3K9, H3K27, H3K36, H3K79, or H4K20 was higher after TNFα stimulation in RASFs vs. OASFs. The gene expression of the 4 HKDMs, including FBXL10, NO66, JMJD2D, and FBXL11, that catalyse the methylation of H3K4, H3K9, or H3K36 was higher after TNFα stimulation in RASFs vs. OASFs.
Conclusions: The study findings suggest that the HKM-modifying enzymes are involved in the alteration of HKM, which results in changes in the gene expression of RASFs.
Similar articles
-
Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts.Sci Rep. 2024 May 9;14(1):10610. doi: 10.1038/s41598-024-60860-7. Sci Rep. 2024. PMID: 38719857 Free PMC article.
-
Histone Methylation and STAT-3 Differentially Regulate Interleukin-6-Induced Matrix Metalloproteinase Gene Activation in Rheumatoid Arthritis Synovial Fibroblasts.Arthritis Rheumatol. 2016 May;68(5):1111-23. doi: 10.1002/art.39563. Arthritis Rheumatol. 2016. PMID: 26713842
-
Epigenetic therapies targeting histone lysine methylation: complex mechanisms and clinical challenges.J Clin Invest. 2024 Oct 15;134(20):e183391. doi: 10.1172/JCI183391. J Clin Invest. 2024. PMID: 39403928 Free PMC article. Review.
-
Induction of RANKL expression and osteoclast maturation by the binding of fibroblast growth factor 2 to heparan sulfate proteoglycan on rheumatoid synovial fibroblasts.Arthritis Rheum. 2004 Aug;50(8):2450-8. doi: 10.1002/art.20367. Arthritis Rheum. 2004. PMID: 15334457
-
The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications.Protein Cell. 2023 Apr 13;14(3):165-179. doi: 10.1093/procel/pwac032. Protein Cell. 2023. PMID: 37051671 Free PMC article. Review.
Cited by
-
Epigenetic Dysregulation in the Pathogenesis of Systemic Lupus Erythematosus.Int J Mol Sci. 2024 Jan 13;25(2):1019. doi: 10.3390/ijms25021019. Int J Mol Sci. 2024. PMID: 38256093 Free PMC article. Review.
-
Epigenetic Regulation Mediated by Methylation in the Pathogenesis and Precision Medicine of Rheumatoid Arthritis.Front Genet. 2020 Aug 4;11:811. doi: 10.3389/fgene.2020.00811. eCollection 2020. Front Genet. 2020. PMID: 32849810 Free PMC article. Review.
-
Multi-Level Analyses of Genome-Wide Association Study to Reveal Significant Risk Genes and Pathways in Neuromyelitis Optica Spectrum Disorder.Front Genet. 2021 Jul 21;12:690537. doi: 10.3389/fgene.2021.690537. eCollection 2021. Front Genet. 2021. PMID: 34367251 Free PMC article.
-
Regulation of cytokine and chemokine expression by histone lysine methyltransferase MLL1 in rheumatoid arthritis synovial fibroblasts.Sci Rep. 2024 May 9;14(1):10610. doi: 10.1038/s41598-024-60860-7. Sci Rep. 2024. PMID: 38719857 Free PMC article.
-
MLL3 Inhibits Apoptosis of Rheumatoid Arthritis Fibroblast-Like Synoviocytes and Promotes Secretion of Inflammatory Factors by Activating CCL2 and the NF-κB Pathway.Inflammation. 2021 Oct;44(5):1803-1814. doi: 10.1007/s10753-021-01459-2. Epub 2021 Apr 29. Inflammation. 2021. PMID: 33914205
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials