<scp>DNMT</scp>1 cooperates with <scp>MBD</scp>4 to inhibit the expression of Glucocorticoid‐induced <scp>TNFR</scp>‐related protein in human T cells

Wang, Shuaiwei; Li, Yangyang; Zhu, Fangming; Lin, Fang; Luo, Xiao‐Zhu; Zhao, Binbin; Zhang, Peng; Li, Dan; Gao, Yayi; Liang, Rui; Liu, Luyan; Tsun, Andy; Yuan, Xiaojun; Wu, Kangning; Li, Bin

doi:10.1002/1873-3468.12690

Cited by 8 publications

(7 citation statements)

References 35 publications

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“…The analysis of two CpGs: −121 bp to +125 bp and in exon 4 in the human Gitr gene, has confirmed total methylation in Tconv due to activation of DNMT1. As expected, Tconv possessed lower Gitr mRNA compared to Tregs and higher binding of DNMT1 and MBD4 to the promoter region [153]. During Tregs thymic maturation, illustrated by the decrease in CD24, it was reported that these cells underwent successive demethylation in the Gitr locus, which can be upregulated by the presence of IL-2 [14].…”

Section: Tnfrsf18 Methylationsupporting

confidence: 58%

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Piotrowska

Gliwiński

Trzonkowski

et al. 2021

IJMS

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Regulatory T cells (Tregs) exert a highly suppressive function in the immune system. Disturbances in their function predispose an individual to autoimmune dysregulation, with a predominance of the pro-inflammatory environment. Besides Foxp3, which is a master regulator of these cells, other genes (e.g., Il2ra, Ctla4, Tnfrsf18, Ikzf2, and Ikzf4) are also involved in Tregs development and function. Multidimensional Tregs suppression is determined by factors that are believed to be crucial in the action of Tregs-related genes. Among them, epigenetic changes, such as DNA methylation, tend to be widely studied over the past few years. DNA methylation acts as a repressive mark, leading to diminished gene expression. Given the role of increased CpG methylation upon Tregs imprinting and functional stability, alterations in the methylation pattern can cause an imbalance in the immune response. Due to the fact that epigenetic changes can be reversible, so-called epigenetic modifiers are broadly used in order to improve Tregs performance. In this review, we place emphasis on the role of DNA methylation of the genes that are key regulators of Tregs function. We also discuss disease settings that have an impact on the methylation status of Tregs and systematize the usefulness of epigenetic drugs as factors able to influence Tregs functions.

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Section: Tnfrsf18 Methylationsupporting

confidence: 58%

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Piotrowska

Gliwiński

Trzonkowski

et al. 2021

IJMS

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“…The same study shows that the combined effect of MBD4 and DNMT1 depletion leads to 100 fold induction of the MSH4 gene, despite the fact that the MSH4 promoter was still methylated. Another study shows that MBD4 and DNMT1 bind to Gitr promotor and their overexpression significantly inhibits Gitr expression [40]. On the other hand MBD4 expression was not significantly different in DNMT1 positive neurons of psychotic patient with history of alcohol abuse [41].…”

Section: Discussionmentioning

confidence: 96%

Changes in the Expression of DNA Methylation Related Genes in Leukocytes of Persons with Alcohol and Drug Dependence

Krasteva

Koycheva

Taseva

et al. 2020

Acta Medica Bulgarica

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Background and objectives. Though numerous studies have shown that the dysregulation of the epigenetic control is involved in disease manifestation, limited data is available on the transcriptional activity of DNA methylation related genes in alcohol and drug addiction. With regard to this, in this study we analyzed the expression levels of genes involved in DNA methylation, including DNMT1, DNMT3a, MeCP2, MBD1, MBD2, MBD3 and MBD4, in blood samples of alcohol and drug dependent persons in comparison to healthy abstainers.Methods. The study included 51 participants: 16 persons with alcohol dependence, 17 persons with drug dependence and 18 clinically healthy controls. To detect the relative mRNA expression levels of the studied genes, Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was applied.Results. Of the seven studied genes, four showed altered expression. MeCP2 and MBD1 were downregulated in the alcohol dependent group (FC = 0.805, p = 0.015 and FC = 0.846, p = 0.034, respectively), while DNMT1 and MBD4 were upregulated in the group with drug dependence (FC = 1.262, p = 0.001 and FC = 1.249, p = 0.005, respectively). No statistically significant changes in the relative mRNA expression were found for DNMT3a, MBD2 and MBD3 genes.Conclusions. Our results are indicative for a role of DNA methylation related genes in alcohol and drug addiction mediated through changes in their transcriptional activity. Studies in this direction will enable better understanding of the underlying mechanisms of addictions supporting the development of more effective therapeutic strategies.

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“…However, it also contributes to the control of T reg fate memory by repressing the transcription of inflammatory genes. Hence, the expression level of DNMT1 to maintain T reg is carefully balanced; overexpression and deficiency both negatively affect T reg numbers, phenotype and functional capacities 54,55 . In line with this, DNA methylation at the Foxp3 locus by DNMT1 restricts Foxp3 expression to CD4 T cells as deletion of DNMT1 fosters the development of CD8 T reg 56 .…”

Section: Installation and Maintenance Of Epigenetic Control Over Treg...mentioning

confidence: 96%

Regulatory T‐cell stability and functional plasticity in health and disease

et al. 2022

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FOXP3-expressing regulatory T cells (T reg ) are indispensable for immune homeostasis and tolerance, and in addition tissue-resident T reg have been found to perform noncanonical, tissue-specific functions. For optimal tolerogenic function during inflammatory disease, T reg are equipped with mechanisms that assure lineage stability. T reg lineage stability is closely linked to the installation and maintenance of a lineage-specific epigenetic landscape, specifically a T regspecific DNA demethylation pattern. At the same time, for local and directed immune regulation T reg must possess a level of functional plasticity that requires them to partially acquire T helper cell (T H ) transcriptional programsthen referred to as T H -like T reg . Unleashing T H programs in T reg , however, is not without risk and may threaten the epigenetic stability of T reg with consequently pathogenic ex-T reg contributing to (auto-) inflammatory conditions. Here, we review how the T reg -stabilizing epigenetic landscape is installed and maintained, and further discuss the development, necessity and lineage instability risks of T H 1-, T H 2-, T H 17-like T reg and follicular T reg .

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DNMT1 cooperates with MBD4 to inhibit the expression of Glucocorticoid‐induced TNFR‐related protein in human T cells

Cited by 8 publications

References 35 publications

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Regulatory T Cells-Related Genes Are under DNA Methylation Influence

Changes in the Expression of DNA Methylation Related Genes in Leukocytes of Persons with Alcohol and Drug Dependence

Regulatory T‐cell stability and functional plasticity in health and disease

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