CCAAT/Enhancer Binding Protein β2 Is Involved in Growth Hormone-Regulated Insulin-Like Growth Factor-II Gene Expression in the Liver of Rainbow Trout (Oncorhynchus mykiss)

被引:5
作者
Lo, Jay H. [1 ]
Chen, Thomas T. [1 ]
机构
[1] Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT 06269 USA
关键词
MESSENGER-RNA; C/EBP-BETA; IGF-I; CHROMATIN-STRUCTURE; HISTONE H1; TRANSCRIPTION; ACETYLATION; ACTIVATION; ALPHA; TELEOST;
D O I
10.1210/en.2009-0960
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Previously, we showed that levels of different CCAAT/enhancer binding protein (C/EBP) mRNAs in the liver of rainbow trout were modulated by GH and suggested that C/EBPs might be involved in GH-induced IGF-II gene expression. As a step toward further investigation, we have developed monospecific polyclonal antibodies to detect rainbow trout C/EBP alpha, -beta 1, -beta 2, and -delta 2 isoform proteins. Injection of GH into adult rainbow trout resulted in a significant increase of C/EBP beta 1, C/EBP beta 2, and C/EBP delta 2 proteins in the liver. Chromatin immunoprecipitation analysis revealed that C/EBP beta 2 binds to multiple sites at the 5' promoter/regulatory region, introns, and the 3' untranslated region of the IGF-II gene. GHtreatment reduced C/EBP beta 2 binding to several of these regions at 6 h after injection. The decreased occupancy of C/EBP beta 2 coincided well with an increase of histone H4 acetylation at the proximal promoter and elevation of the IGF-II mRNA level. Immunoblotting analysis showed that C/EBP beta 2 existed predominately as a truncated form in the liver, and cotransfection analysis further showed that the truncated C/EBP beta 2 acted as a negative regulator on IGF-II proximal promoter. GH treatment caused deacetylation of C/EBP beta 2 in the liver. In addition, weobserved a GH-dependent interaction of C/EBP beta 2 with a complex involving histone H1. All together, these results suggest that C/EBP beta 2 was regulated at multiple levels by GH, and C/EBP beta 2 may play a suppressive role in mediating GH-induced IGF-II expression in the liver of rainbow trout. (Endocrinology 151: 2128-2139, 2010)
引用
收藏
页码:2128 / 2139
页数:12
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