AP2-like cis element is required for calretinin gene promoter activity in cells of neuronal phenotype differentiated from multipotent human cell line DEV

Billing-Marczak, Katarzyna; Bużañska, Leonora; Winsky, Lois; Nowotny, Marcin; Rudka, Tomasz; Isaacs, Krystyna R.; Belin, M. F.; Kuźnicki, Jacek

doi:10.1016/s0167-4781(02)00443-8

Cited by 13 publications

(12 citation statements)

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“…The −161/ + 80bp fragment of the CALB2 promoter was identified as the minimal element resulting in sustained transcriptional activity in all tested mesothelioma cell lines. This is consistent with the previously defined minimal mouse Calb2 promoter (−115/ + 54bp) shown to be active in rat cortical neuronal cells, rat cerebellar granule cells, colon adenocarcinoma (WiDr) and mesothelioma cells (SPC111) [13, 14]. Moreover, we found that the transcriptional activity of the −161/ + 80bp CALB2 promoter reporter was highly correlated with CALB2 expression levels.…”

Section: Discussionsupporting

confidence: 92%

“…It has been reported that the mouse Calb2 and human CALB2 promoter region contain TATA and CAAT boxes [12]. A mouse Calb2 promoter fragment (−115/ + 54bp) was shown to be active in neuronal and cancer cells [13, 14]. In human colon cancer cells, calretinin expression is downregulated by butyrate, a substance that induces cell differentiation [15].…”

Section: Introductionmentioning

confidence: 99%

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Identification ofcis-andtrans-acting elements regulating calretinin expression in mesothelioma cells

et al. 2016

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Calretinin (CALB2) is a diagnostic marker for epithelioid mesothelioma. It is also a prognostic marker since patients with tumors expressing high calretinin levels have better overall survival. Silencing of calretinin decreases viability of epithelioid mesothelioma cells. Our aim was to elucidate mechanisms regulating calretinin expression in mesothelioma. Analysis of calretinin transcript and protein suggested a control at the mRNA level. Treatment with 5-aza-2′-deoxycytidine and analysis of TCGA data indicated that promoter methylation is not likely to be involved. Therefore, we investigated CALB2 promoter by analyzing ~1kb of genomic sequence surrounding the transcription start site (TSS) + 1 using promoter reporter assay. Deletion analysis of CALB2 proximal promoter showed that sequence spanning the −161/+80bp region sustained transcriptional activity. Site-directed analysis identified important cis-regulatory elements within this −161/+80bp CALB2 promoter. EMSA and ChIP assays confirmed binding of NRF-1 and E2F2 to the CALB2 promoter and siRNA knockdown of NRF-1 led to decreased expression of calretinin. Cell synchronization experiment showed that calretinin expression was cell cycle regulated with a peak of expression at G1/S phase. This study provides the first insight in the regulation of CALB2 expression in mesothelioma cells.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Identification ofcis-andtrans-acting elements regulating calretinin expression in mesothelioma cells

et al. 2016

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“…59 The AP2 TF family includes members of AP2-a, b, and g. AP2 acts as a transcriptional activator, and is thought to play a role in modulating neuron-and epithelium-specific genes. 60,61 Our results also suggest that c-Jun may be important for transcriptional activation of HTR1B in HCN-1A cells, and that the active TF complex may not contain c-Fos. However, further experiments are needed to definitively demonstrate which AP1 TFs might be involved in the formation of the observed transcriptional complexes at the AÀ161T site.…”

Section: Discussionmentioning

confidence: 53%

Polymorphisms in the 5′-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

et al. 2003

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We present evidence of complex balancing regulation of HTR1B transcription by common polymorphisms in its promoter. Computational analysis of the HTR1B gene predicted that a 5 0 segment, spanning common DNA sequence variations, TÀ261G, AÀ161T, and À182INS/ DELÀ181, contained a putative functional promoter. Using a secreted alkaline phosphatase (SEAP) reporter gene system, we found that the haplotype À261G_À182INSÀ181_AÀ161 enhanced transcriptional activity 2.3-fold compared with the haplotype TÀ261_À182INSÀ181_AÀ161. Conversely, À161T reversed this, and the net effect when À261G and À161T were in the same haplotype (À261G_À182INSÀ181_À161T) was equivalent to the major haplotype (TÀ261_À182INSÀ181_AÀ161). Electrophoretic mobility shift experiments showed that À261G and À161T modify the binding of transcription factors (TFs): À261G generates a new AP2 binding site, while alleles AÀ161 and À161T exhibit different binding characteristics to AP1. TÀ261G and AÀ161T were found to be in linkage disequilibrium (LD) with G861C in a European ancestry population. Interestingly, G861C has been reported to be associated with several psychiatric disorders. Our results indicate that HTR1B is the target of substantial transcriptional genetic regulation by common haplotypes, which are in LD with the HTR1B single-nucleotide polymorphism (SNP) most commonly used in association studies. Molecular Psychiatry (2003) 8, 901-910.

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“…The adipose H6PDH mRNA levels in aP2-H6PDH Tg mice are comparable to or slightly higher than that in adipose tissue of obese rodents and diabetic humans, suggesting that the phenotypic changes found in aP2-H6PDH Tg mice are physiologically and pathologically relevant. However, the aP2 promoter is not exclusively fat-specific; it is also reported to be expressed in macrophages and brains (4,27), supporting the possibility that nonadipocyte expression of H6PDH may have contributed to their observed phenotype, although H6PDH Tg mice did not have altered hypothalamic H6PDH mRNA levels. Thus it is unlikely that nonadipocyte H6PDH gene expression accounts for the phenotype observed with H6PDH Tg mice.…”

Section: Discussionmentioning

confidence: 94%

Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice

Wang

Liu

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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The prereceptor activation of glucocorticoid production in adipose tissue by NADPH-dependent 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1) has emerged as a potential mechanism in the pathogenesis of visceral obesity and metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) is an endoplasmic reticulum lumen-resident enzyme that generates cofactor NADPH and thus mediates 11␤-HSD1 activity. To determine the role of adipose H6PDH in the prereceptor modulation of 11␤-HSD1 and metabolic phenotypes, we generated a transgenic (Tg) mouse model overexpressing H6PDH under the control of the enhancerpromoter region of the adipocyte fatty acid-binding protein (aP2) gene (aP2/H6PDH Tg mice). Transgenic aP2/H6PDH mice exhibited relatively high expression of H6PDH and elevated corticosterone production with induction of 11␤-HSD1 activity in adipose tissue. This increase in corticosterone production in aP2-H6PDH Tg mice resulted in mild abdominal fat accumulation with induction of C/EBP mRNA expression and slight weight gain. Transgenic aP2/H6PDH mice also exhibited fasting hyperglycemia and glucose intolerance with insulin resistance. In addition, the aP2/H6PDH Tg mice have elevated circulating free fatty acid levels with a concomitant increased adipose lipolytic action associated with elevated HSL mRNA and Ser 660 HSL phosphorylation within abdominal fat. These results suggest that increased H6PDH expression specifically in adipose tissue is sufficient to cause intra-adipose glucocorticoid production and adverse metabolic phenotypes. These findings suggest that the aP2/H6PDH Tg mice may provide a favorable model for studying the potential impact of H6PDH in the pathogenesis of human metabolic syndrome.11␤-hydroxysteroid dehydrogenase type 1; transgenic mouse VISCERAL FAT DEPOSITION IS FREQUENTLY ASSOCIATED with metabolic syndrome, including visceral obesity, insulin resistance, hypertension, and dyslipidemia (13,22,39). However, the underlying mechanisms of these metabolic perturbations are poorly understood. Patients with glucocorticoid (GC) excess (Cushing's syndrome) promote visceral fat deposition and develop metabolic syndrome (1, 21). In adipose tissue, GCs promote lipolysis by stimulating two key enzymes, hormonesensitive lipase (HSL) and adipose triglyceride lipase (ATGL), to increase hydrolysis of triacylglycerol and release free fatty acids (FFA) in the circulation that is linked to hyperlipidemia and global insulin resistance (8, 24, 46). However, tissuespecific GC availability is regulated by an intracellular endoplasmic reticulum (ER) lumen-resident enzyme, 11␤-hydroxysteroid dehydrogenase type 1 (11␤-HSD1), that converts inert cortisone (11-dehydrocorticosterone in rodents) to the active glucocorticoid receptor (GR)-ligand cortisol (corticosterone in rodents) and thereby amplifies intracellular GC reproduction, particularly in adipose tissues (7,41,23,33). Increased adipose GC activation by 11␤-HSD1 leads to visceral obesity and features of the metabolic syndrome (29). Prereceptor amplification of GC ...

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AP2-like cis element is required for calretinin gene promoter activity in cells of neuronal phenotype differentiated from multipotent human cell line DEV

Cited by 13 publications

References 40 publications

Identification ofcis-andtrans-acting elements regulating calretinin expression in mesothelioma cells

Identification ofcis-andtrans-acting elements regulating calretinin expression in mesothelioma cells

Polymorphisms in the 5′-untranslated region of the human serotonin receptor 1B (HTR1B) gene affect gene expression

Transgenic overexpression of hexose-6-phosphate dehydrogenase in adipose tissue causes local glucocorticoid amplification and lipolysis in male mice

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