1. TET1 is an important transcriptional activator of TNFα expression in macrophages.
- Author
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Sun, Fangfang, Abreu-Rodriguez, Irene, Ye, Shuang, Gay, Steffen, Distler, Oliver, Neidhart, Michel, and Karouzakis, Emmanuel
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EPIGENOMICS , *DEVELOPMENTAL biology , *GENE expression , *LEUCOCYTES , *CYTOLOGY , *MACROPHAGE activation - Abstract
Activation of macrophages and overexpression of TNFα is associated with the pathogenesis of chronic inflammatory diseases. However, the mechanisms leading to TNFα overexpression are still unknown. 5-methylocytosine (5-mC) is an epigenetic modification that is associated with silenced genes. Recent studies showed that it is converted to 5-hydroxylmethylocytosine (5-hmC) and reactivates gene expression through the action of the family of Ten-Eleven-Translocation (TET1-3) enzymes. In this study, we show that 5-hmC levels are increased globally and specifically in the TNFα promoter during the differentiation of monocytes to macrophages. In addition, the levels of 5-hmC are increased upon LPS stimulation of macrophages. Furthermore, CRIPSR stable knockout of TET1 decreases the expression of TNFα and other pro-inflammatory cytokines. In conclusion, we showed that TET1 contributes to the activation of macrophages possibly through regulation of 5-hydroxymethylation in the promoter of pro-inflammatory cytokine genes. The TET1 enzyme could be a promising therapeutic target to inhibit the persistent inflammation caused by macrophages in chronic inflammatory diseases. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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