Interleukin-6 represses the transcription of the CCAAT/enhancer binding protein-  gene in hepatoma cells by inhibiting its ability to autoactivate the proximal promoter region

The ovulatory LH surge induces rapid up-regulation of Cyp11a1 in granulosa cells (GCs) undergoing luteinization during ovulation. This study investigated in vivo whether epigenetic controls including histone modifications and DNA methylation in the promoter region are associated with the rapid increase of Cyp11a1 gene expression after LH surge. GCs were obtained from rats treated with equine chorionic gonadotropin (CG) before (0 h) and 4 h and 12 h after human (h)CG injection. Cyp11a1 mRNA levels rapidly increased after hCG injection, reached a peak at 4 hours, and then remained elevated until 12 hours. DNA methylation status in the Cyp11a1 proximal promoter region was hypomethylated and did not change at any of the observed times after hCG injection. Chromatin immunoprecipitation assays revealed that the levels of trimethylation of lysine 4 on histone H3 (H3K4me3), an active mark for transcription, increased, whereas the levels of H3K9me3 and H3K27me3, which are marks associated with repression of transcription, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin condensation, which was analyzed using deoxyribonuclease I, decreased in the Cyp11a1 proximal promoter after hCG injection. Chromatin immunoprecipitation assays also showed that the binding activity of CAATT/enhancer-binding protein-β to the Cyp11a1 proximal promoter increased after hCG injection. Luciferase assays revealed that the CAATT/enhancer-binding protein-β-binding site had transcriptional activity and contributed to basal and cAMP-induced Cyp11a1 expression. These results suggest that changes in histone modification and chromatin structure in the Cyp11a1 proximal promoter are involved in the rapid increase of Cyp11a1 gene expression in GCs undergoing luteinization during ovulation.

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Regulation of rabbit alpha1-acid glycoprotein gene expression in acute-phase liver. Identification of inducible and constitutive proteins like CCAAT-enhancer binding protein that interact with the 5'-proximal promoter elements

European Journal of Biochemistry ◽

10.1111/j.1432-1033.1993.tb18124.x ◽

1993 ◽

Vol 216 (1) ◽

pp. 127-136 ◽

Cited By ~ 7

Author(s):

Bimal K. RAY ◽

Xiong GAO ◽

Alpana RAY

Keyword(s):

Gene Expression ◽

Acute Phase ◽

Binding Protein ◽

Proximal Promoter ◽

Promoter Elements ◽

Acid Glycoprotein ◽

Glycoprotein Gene ◽

Enhancer Binding Protein ◽

Ccaat Enhancer Binding Protein

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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)

Endocrinology ◽

10.1210/en.2009-0960 ◽

2010 ◽

Vol 151 (5) ◽

pp. 2128-2139 ◽

Cited By ~ 4

Author(s):

Jay H. Lo ◽

Thomas T. Chen

Keyword(s):

Gene Expression ◽

Rainbow Trout ◽

Binding Protein ◽

Regulatory Region ◽

Negative Regulator ◽

Proximal Promoter ◽

Gh Treatment ◽

Enhancer Binding Protein ◽

Histone H4 Acetylation ◽

Ccaat Enhancer Binding Protein

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/EBPα, -β1, -β2, and -δ2 isoform proteins. Injection of GH into adult rainbow trout resulted in a significant increase of C/EBPβ1, C/EBPβ2, and C/EBPδ2 proteins in the liver. Chromatin immunoprecipitation analysis revealed that C/EBPβ2 binds to multiple sites at the 5′ promoter/regulatory region, introns, and the 3′ untranslated region of the IGF-II gene. GH treatment reduced C/EBPβ2 binding to several of these regions at 6 h after injection. The decreased occupancy of C/EBPβ2 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/EBPβ2 existed predominately as a truncated form in the liver, and cotransfection analysis further showed that the truncated C/EBPβ2 acted as a negative regulator on IGF-II proximal promoter. GH treatment caused deacetylation of C/EBPβ2 in the liver. In addition, we observed a GH-dependent interaction of C/EBPβ2 with a complex involving histone H1. All together, these results suggest that C/EBPβ2 was regulated at multiple levels by GH, and C/EBPβ2 may play a suppressive role in mediating GH-induced IGF-II expression in the liver of rainbow trout.

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