Histone modifications on the adrenergic induction of type II deiodinase in rat pinealocytes.

Histone modifications have been shown to play an important role in regulating gene expression. In this study, we investigated the impact of histone modifications on the adrenergic-regulated transcription of type 2 deiodinase (Dio2), a CREB-target gene in the rat pinealocyte. Treatment of pinealocytes with inhibitors of aurora C, a histone kinase, resulted in an inhibitory effect on the adrenergic-stimulated histone H3 Ser10 phosphorylation and Dio2 transcription. Given the established link between histone phosphorylation and acetylation, the role of histone acetylation on the adrenergic-induced Dio2 transcription was investigated. Treatment of pinealocytes with histone deacetylase inhibitors inhibited the adrenergic-induced Dio2 transcription. Chromatin immunoprecipitation with antibodies against acetylated Lys14 of H3 showed an increase in DNA recovery of the promoter region of Dio2 following treatment with trichostatin A. Together, our results indicate that, beside activation of CREB, epigenetic factors such as histone modifications also play an important role in regulating Dio2 transcription.