scholarly journals Hypomethylation of ETS Transcription Factor Binding Sites and Upregulation of PARP1 Expression in Endometrial Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Fang-Fang Bi ◽  
Da Li ◽  
Qing Yang
Keyword(s):  
Endometrial Cancer ◽  
Cancer Progression ◽  
Promoter Region ◽  
Core Promoter ◽  
Histological Grade ◽  
Endometrial Adenocarcinoma ◽  
Mrna Levels ◽  
Core Promoter Region ◽  
The Core ◽  
Cpg Sites

Although PARP1 promoter methylation is involved in the regulation of PARP1 expression in human keratinocyte lines and lymphoblastoid cell lines, its roles in human endometrial cancer are unknown. DNA from forty normal endometrium (NE) and fifty endometrial adenocarcinoma (EAC) tissues were analyzed by bisulfite sequencing using primers focusing on the core promoter region of PARP1. Expression levels of PARP1 were assessed by immunohistochemistry and real-time PCR. Associations between patient clinicopathological characteristics and PARP1 protein levels were assessed by Fisher’s exact test. Here, PARP1 mRNA and protein were overexpressed in EAC tissues(P<0.05). CpG sites within the ETS motif in the PARP1 promoter exhibited significant hypomethylation in EAC tissues, and there was a significant negative correlation between PARP1 mRNA levels and the number of methylated sites in both NE and EAC tissues (R2=0.262,P<0.001). Notably, PARP1 protein expression was associated with FIGO stage(P=0.026), histological grade(P=0.002), and body mass index(P=0.04). Our findings imply that PARP1 overexpression may participate in endometrial cancer progression, and abnormal hypomethylation of CpG sites within the ETS motif in the core promoter region may be responsible for PARP1 overexpression in EAC tissues.

scholarly journals The core promoter region of the tumor necrosis factor alpha gene confers phorbol ester responsiveness to upstream transcriptional activators.

1992 ◽  
Vol 12 (3) ◽  
pp. 1352-1356 ◽  
Author(s):  
D C Leitman ◽  
E R Mackow ◽  
T Williams ◽  
J D Baxter ◽  
B L West
Keyword(s):  
Transcription Factors ◽  
Tumor Necrosis Factor ◽  
Promoter Region ◽  
Tumor Necrosis ◽  
Core Promoter ◽  
Core Promoter Region ◽  
Necrosis Factor Alpha ◽  
The Core ◽  
Factor Alpha ◽  
Necrosis Factor

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.

scholarly journals High Frequency of Either Altered Pre-Core Start Codon or Weakened Kozak Sequence in the Core Promoter Region in Hepatitis B Virus A1 Strains from Rwanda

Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 182 ◽  
Author(s):  
Heléne Norder ◽  
Theogene Twagirumugabe ◽  
Joanna Said ◽  
Yarong Tian ◽  
Ka-Wei Tang ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Promoter Region ◽  
Core Promoter ◽  
Etiologic Agent ◽  
Start Codon ◽  
Core Promoter Region ◽  
Kozak Sequence ◽  
The Core ◽  
B Virus

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.

Mutations in the core promoter region of hepatitis B virus in patients with chronic hepatitis B

1996 ◽  
Vol 49 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Masayuki Kurosaki ◽  
Nobuyuki Enomoto ◽  
Yasuhiro Asahina ◽  
Ikuo Sakuma ◽  
Takaaki Ikeda ◽  
...  
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Promoter Region ◽  
Core Promoter ◽  
Core Promoter Region ◽  
The Core ◽  
B Virus

Naturally occurring hepatitis B virus mutants with deletions in the core promoter region

1994 ◽  
Vol 20 (6) ◽  
pp. 837-841 ◽  
Author(s):  
Tomasz Laskus ◽  
Jorge Rakela ◽  
Myron J. Tong ◽  
Marek J. Nowicki ◽  
James W. Mosley ◽  
...  
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Promoter Region ◽  
Core Promoter ◽  
Core Promoter Region ◽  
The Core ◽  
Naturally Occurring ◽  
B Virus

scholarly journals Methylation in the Core-promoter Region of the Chondromodulin-I Gene Determines the Cell-specific Expression by Regulating the Binding of Transcriptional Activator Sp3

2004 ◽  
Vol 279 (27) ◽  
pp. 28789-28797 ◽  
Author(s):  
Tomoki Aoyama ◽  
Takeshi Okamoto ◽  
Satoshi Nagayama ◽  
Koichi Nishijo ◽  
Tatsuya Ishibe ◽  
...  
Keyword(s):  
Promoter Region ◽  
Core Promoter ◽  
Transcriptional Activator ◽  
Core Promoter Region ◽  
Specific Expression ◽  
The Core ◽  
I Gene

scholarly journals The Core Promoter Is a Regulatory Hub for Developmental Gene Expression

2021 ◽  
Vol 9 ◽  
Author(s):  
Anna Sloutskin ◽  
Hila Shir-Shapira ◽  
Richard N. Freiman ◽  
Tamar Juven-Gershon
Keyword(s):  
Gene Expression ◽  
Transcriptional Activation ◽  
Transcription Initiation ◽  
Promoter Region ◽  
Core Promoter ◽  
Developmental Gene ◽  
Core Promoter Region ◽  
Developmental Gene Expression ◽  
The Core ◽  
Regulatory Module

The development of multicellular organisms and the uniqueness of each cell are achieved by distinct transcriptional programs. Multiple processes that regulate gene expression converge at the core promoter region, an 80 bp region that directs accurate transcription initiation by RNA polymerase II (Pol II). In recent years, it has become apparent that the core promoter region is not a passive DNA component, but rather an active regulatory module of transcriptional programs. Distinct core promoter compositions were demonstrated to result in different transcriptional outputs. In this mini-review, we focus on the role of the core promoter, particularly its downstream region, as the regulatory hub for developmental genes. The downstream core promoter element (DPE) was implicated in the control of evolutionarily conserved developmental gene regulatory networks (GRNs) governing body plan in both the anterior-posterior and dorsal-ventral axes. Notably, the composition of the basal transcription machinery is not universal, but rather promoter-dependent, highlighting the importance of specialized transcription complexes and their core promoter target sequences as key hubs that drive embryonic development, differentiation and morphogenesis across metazoan species. The extent of transcriptional activation by a specific enhancer is dependent on its compatibility with the relevant core promoter. The core promoter content also regulates transcription burst size. Overall, while for many years it was thought that the specificity of gene expression is primarily determined by enhancers, it is now clear that the core promoter region comprises an important regulatory module in the intricate networks of developmental gene expression.

scholarly journals Molecular Characterization of the eis Promoter of Mycobacterium tuberculosis

2004 ◽  
Vol 186 (16) ◽  
pp. 5410-5417 ◽  
Author(s):  
Esteban A. Roberts ◽  
Amanda Clark ◽  
Sarah McBeth ◽  
Richard L. Friedman
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Promoter Region ◽  
Core Promoter ◽  
Random Mutagenesis ◽  
Core Promoter Region ◽  
E Coli ◽  
The Core ◽  
Upstream Promoter ◽  
Promoter Deletion Analysis ◽  
Group A

ABSTRACT To further understand Mycobacterium tuberculosis pathogenesis, the regulation of potential virulence genes needs to be investigated. The eis gene of M. tuberculosis H37Rv enhances the intracellular survival of Mycobacterium smegmatis, which does not contain eis, within macrophages (J. Wei, J. L. Dahl, J. W. Moulder, E. A. Roberts, P. O'Gaora, D. B. Young, and R. L. Friedman, J. Bacteriol. 182:377-384, 2000). Experiments were done to characterize the eis promoter in M. smegmatis and M. tuberculosis H37Ra. The putative −10 and −35 regions matched the Escherichia coli σ70 consensus 67 and 83%, respectively, making it a group A/SigA-like mycobacterial promoter. Expression of site-directed variants of the core promoter region, determined by flow cytometry using gfp as a reporter, showed that the putative −10 region is essential for eis expression. In addition, site-directed alteration of the eis promoter to the consensus E. coli σ70 promoter elements increased gfp transcription to levels similar to that driven by the heat shock promoter, phsp60, of Mycobacterium bovis BCG. Upstream promoter deletion analysis showed that a 200- and 412-bp region of the promoter was necessary for maximum expression of gfp in M. smegmatis and M. tuberculosis H37Ra, respectively. Random mutagenesis of the 412-bp eis promoter, using a catechol 2,3-dioxygenase screen and activity assay, defined nucleotides upstream of the core promoter region that are essential to eis expression in both M. smegmatis and M. tuberculosis H37Ra, including a region homologous to a DinR cis element.

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