Open AccessEffects of H3 and H4 Histones Acetylation and Bindings of CREB Binding Protein and p300 at the Promoter on Hepatic Expression of γ-glutamyltransferase Gene in a Streptozotocin-Induced Moderate Hypoinsulinemic Rat Model
Author(s) -
Tatsuhide Tanaka,
Takakazu Mizuno,
Tomoyuki Nakagawa,
T. Hayakawa,
Mikio Shimada
Publication year - 2021
Publication title -
physiological research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.647
H-Index - 70
eISSN - 1802-9973
pISSN - 0862-8408
DOI - 10.33549/physiolres.934620
Subject(s) - acetylation , histone , endocrinology , streptozotocin , medicine , creb , histone h4 , histone h3 , chemistry , gene expression , biology , microbiology and biotechnology , gene , biochemistry , diabetes mellitus , transcription factor
Gamma-glutamyltransferase (GGT), a marker of liver disease, has been shown to be associated with increased risk of diabetes and relative insulin secretion deficiency. However, the mechanism of hepatic Ggt regulation has not been explored fully. In this study, we made a concerted effort to understand the mechanism by investigating the effects of acetylation of histones H3 and H4, and bindings of histone acetyltransferases, CREB binding protein (CBP) and p300, at the Ggt promoter on the regulation of the expression of Ggt gene in the livers of streptozotocin (STZ)-induced moderate hypoinsulinemia rat model. The rats treated with STZ showed remarkably higher serum GGT level and hepatic Ggt/GGT expression than the untreated control rats. Furthermore, the acetylation of histones H3 and H4, and the binding of CBP not p300 at the Ggt promoter regions were significantly higher in the livers of STZ rats than those of the control rats. These results suggest that an enhanced hepatic expression of Ggt is associated with increased acetylation of histones H3 and H4 and CBP binding at the Ggt promoter in STZ-induced moderate hypoinsulinemic rats.