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Abstract
RGS10 (regulator of G-protein signaling) is a GTPase accelerating protein which increases the rate of hydrolysis of GTP bound to G subunit (active) into GDP bound form (inactive) thereby inactivating G-protein signaling. RGS10 is enriched in microglia and is a key regulator of pro-inflammatory cytokine production. Previous studies suggest that epigenetic mechanisms involving histone deacetylases (HDACs) regulate the expression of RGS10. HDAC1 has been shown to be bound with RGS10 promoter region and histone H3 proteins are deacetylated at the RGS10 proximal promoter when microglia are stimulated with LPS. Pharmacological inhibition of HDACs using broad spectrum HDAC inhibitors has been shown to block LPS induced suppression of RGS10 in microglia. The aim of this study is to identify the specific HDAC isoforms involved in the epigenetic regulation of RGS10 in microglia by using selective HDAC inhibitors and evaluate the role of HDAC1 in regulation of RGS10 by using HDAC1 siRNA.