Glioma-induced SIRT1-dependent activation of hMOF histone H4 lysine 16 acetyltransferase in microglia promotes a tumor supporting phenotype.

ABSTRACT: High-grade gliomas are malignant aggressive primary brain tumors with limited therapeutic options, and dismal prognosis for patients. Microglia, the resident immune cells of the brain, are recruited and reprogrammed into tumor-supporting cells by glioma cells, which in turn positively influence tumor expansion and infiltration into surrounding brain tissues. Here, we report that glioma-induced microglia conversion is coupled to an increase of histone H4 lysine 16 (H4K16) acetylation level in microglia, through increased nuclear localization of the deacetylase SIRT1, which in turn results in deacetylation of the H4K16 acetyltransferase hMOF and its recruitment to the chromatin at promoter regions of microglial target genes. Furthermore, we demonstrate that manipulation of the microglial H4K

SUBMITTER: Saidi D 

PROVIDER: S-EPMC5749650 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature