scholarly journals 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 ◽  
2010 ◽  
Vol 151 (5) ◽  
pp. 2128-2139 ◽  
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.

scholarly journals CCAAT/enhancer-binding protein β represses human papillomavirus 11 upstream regulatory region expression through a promoter-proximal YY1-binding site

2006 ◽  
Vol 87 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Walter M. Ralph ◽  
Kai Liu ◽  
Karen J. Auborn
Keyword(s):  
Gene Expression ◽  
Human Papillomavirus ◽  
Binding Site ◽  
Binding Protein ◽  
Regulatory Region ◽  
Upstream Regulatory Region ◽  
Expression Plasmid ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Exogenous Expression

CCAAT/enhancer-binding protein β (C/EBPβ) can function as a repressor or as an activator of human papillomavirus (HPV) gene expression, depending on which cell type the experiments are conducted. In this report, it was shown that within primary human foreskin keratinocyte cells (HFK) the activity of C/EBPβ can be switched from that of a repressor of HPV11 expression to an activator by mutating a single promoter-proximal consensus YY1-binding site within the HPV11 upstream regulatory region (URR). It was shown that in HFK cells, exogenous expression of C/EBPβ significantly activates the expression of mutant HPV11 URR reporter plasmids that contain deletions which overlap a 127 bp region (−269 to −142). Inclusive in this region are binding sites for multiple transcription factors, including AP1, YY1 and C/EBPα. Only mutation of the YY1 site resulted in the switch in phenotype, indicating that C/EBPβ represses HPV11 expression in these cells via YY1 binding. The level of YY1 activity was also measured in HFK cells transfected with a C/EBPβ expression plasmid and a significant increase in YY1 activity as compared with mock-transfected cells was found. C33A cells, which exhibit activation of wild-type HPV11 gene expression with exogenous C/EBPβ co-expression, failed to demonstrate C/EBPβ-induced YY1 activation. It was concluded that in HFK cells, exogenous C/EBPβ induces the activity of YY1, which, in turn, can repress HPV11 URR expression through the promoter-proximal YY1-binding site.

DDRE-30. CELL-PENETRATING PEPTIDE ANTAGONIST OF CCAAT/ENHANCER BINDING PROTEIN ß DISPLAYS POTENT ANTI-GLIOBLASTOMA ACTIVITY

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi80-vi81
Author(s):  
Jim Rotolo ◽  
Lila Ghamsari ◽  
Ricardo Ramierez ◽  
Mark Koester ◽  
Siok Leong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Leucine Zipper ◽  
Binding Protein ◽  
Xenograft Model ◽  
Mesenchymal Transition ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Subcutaneous Xenograft ◽  
Peptide Antagonist ◽  
Anti Tumor Activity

Abstract CCAAT/Enhancer Binding Protein Beta (C/EBPß) is a transcription factor overexpressed in glioblastoma (GBM). Mechanistically, C/EBPß is a master regulator of mesenchymal transition in GBM, and its increased expression correlates with mesenchymal differentiation and predicts poor clinical outcome. C/EBPß activity requires dimerization with co-factors such as CREB/ATF family members via leucine zipper interactions. ST101 is a novel peptide antagonist of C/EBPß currently being evaluated in a Phase 1/2 clinical study in patients with advanced unresectable and metastatic solid tumors. ST101 binds to the C/EBPß leucine zipper, thereby preventing dimer formation and inhibiting its transcriptional activity, resulting in selective tumor cell cytotoxicity. Here, we describe ST101 non-clinical anti-tumor activity against GBM. In vitro studies in T98G and U251 cells demonstrate ST101 dose-dependent impact of cell viability (EC50 of 2.2 and 1.2 μM, respectively), accompanied by significant impact on C/EBPß-mediated gene expression as determined by qPCR analysis. In contrast, normal human mononuclear and epithelial cells were not sensitive to ST101 (EC50 > 80 μM). In vivo, ST101 displayed significant anti-tumor activity in a U251 GBM subcutaneous xenograft model, resulting in 81.4% tumor growth inhibition (TGI) vs. control and undetectable tumors in 50% of animals. Following ST101 exposure tumors displayed reduced BIRC3 and ID2 gene expression, and significantly increased cleaved caspase 3 immunostaining indicative of cell death induction. In U251 tumors, subtherapeutic ST101 (< 5% TGI) in combination with temozolomide (< 5% TGI) resulted in 52.8% TGI, significantly greater than either single-agent alone. Similarly, in a temozolomide-refractory T98G GBM subcutaneous xenograft model, ST101 (41.6% TGI) in combination with TMZ (< 5% TGI) resulted in significant anti-GBM response (72.4% TGI). These data emphasize the potential of ST101 as a potent peptide therapeutic for GBM.

scholarly journals Gene Expression of CCAAT/Enhancer-Binding Protein .DELTA. Mediated by Autoregulation Is Repressed by Related Gene Family Proteins.

2000 ◽  
Vol 23 (12) ◽  
pp. 1424-1429 ◽  
Author(s):  
Atsuhiro TANABE ◽  
Chizumi KUMAHARA ◽  
Shigehiro OSADA ◽  
Tsutomu NISHIHARA ◽  
Masayoshi IMAGAWA
Keyword(s):  
Gene Expression ◽  
Gene Family ◽  
Binding Protein ◽  
Related Gene ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein

CCAAT/enhancer binding protein δ regulates glial proinflammatory gene expression

2013 ◽  
Vol 34 (9) ◽  
pp. 2110-2124 ◽  
Author(s):  
Tony Valente ◽  
Marco Straccia ◽  
Nuria Gresa-Arribas ◽  
Guido Dentesano ◽  
Josep M. Tusell ◽  
...  
Keyword(s):  
Gene Expression ◽  
Binding Protein ◽  
Enhancer Binding Protein ◽  
Ccaat Enhancer Binding Protein ◽  
Proinflammatory Gene ◽  
Proinflammatory Gene Expression

scholarly journals Epigenetic Changes of the Cyp11a1 Promoter Region in Granulosa Cells Undergoing Luteinization During Ovulation in Female Rats

Endocrinology ◽  
2016 ◽  
Vol 157 (9) ◽  
pp. 3344-3354 ◽  
Author(s):  
Maki Okada ◽  
Lifa Lee ◽  
Ryo Maekawa ◽  
Shun Sato ◽  
Takuya Kajimura ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Granulosa Cells ◽  
Chromatin Immunoprecipitation ◽  
Promoter Region ◽  
Binding Protein ◽  
Female Rats ◽  
Proximal Promoter ◽  
Lh Surge ◽  
Enhancer Binding Protein

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.

Sign in / Sign up

Export Citation Format

Share Document