Class Ⅰ histone deacetylase inhibitor regulate of Mycobacteria-Driven guanylate-binding protein 1 gene expression

Abstract

Guanylate-binding proteins (GBPs) are a class of interferon (IFN)-stimulated genes with well-established activity against viruses, intracellular bacteria, and parasites. The effect of epigenetic modification on GBP activity upon Mycobacterium tuberculosis (Mtb) infection is poorly understood. In this study, we found that Mtb infection can significantly increase the expression of GBPs. Class Ⅰ histone deacetylase inhibitor (HDACi) MS-275 can selectively inhibit GBP1 expression, ultimately affecting the release of inflammatory cytokines IL-1β and suppressing Mtb intracellular survival. Moreover, interfering with GBP1 expression could reduce the production of IL-1β and the level of cleaved-caspase-3 in response to Mtb infection. GBP1 silencing did not affect Mtb survival. Besides, using the bisulfite sequencing PCR, we showed that the CpG site of the GBP1 promoter was hypermethylated, and the methylation status of the GBP1 promoter did not change significantly upon Mtb infection. Overall, this study sheds light on the role of GBP in Mtb infection and provides a link between epigenetics and GBP1 activity.

Keywords: Epigenetic modification; Guanylate-binding protein; Histone deacetylases inhibitor; Mycobacterium tuberculosis.