Transport Function and Transcriptional Regulation of a Liver-Enriched Human Organic Anion Transporting Polypeptide 2B1 Transcriptional Start Site Variant

2013 ◽  
Vol 83 (6) ◽  
pp. 1218-1228 ◽  
Author(s):  
Michael J. Knauer ◽  
Anthea J. Girdwood ◽  
Richard B. Kim ◽  
Rommel G. Tirona
Keyword(s):  
Transcriptional Regulation ◽  
Transcriptional Start Site ◽  
Organic Anion ◽  
Start Site ◽  
Transport Function ◽  
Organic Anion Transporting Polypeptide

scholarly journals Protein Kinase A and Mitogen-Activated Protein Kinase Pathways Antagonistically Regulate Fission Yeast fbp1Transcription by Employing Different Modes of Action at Two Upstream Activation Sites

2000 ◽  
Vol 20 (17) ◽  
pp. 6426-6434 ◽  
Author(s):  
Lori A. Neely ◽  
Charles S. Hoffman
Keyword(s):  
Signal Transduction ◽  
Transcriptional Regulation ◽  
Protein Kinase ◽  
Mapk Pathway ◽  
Transcriptional Start Site ◽  
Mitogen Activated Protein Kinase ◽  
Signal Transduction Pathways ◽  
Start Site ◽  
Mitogen Activated Protein ◽  
Kinase A

ABSTRACT A significant challenge to our understanding of eukaryotic transcriptional regulation is to determine how multiple signal transduction pathways converge on a single promoter to regulate transcription in divergent fashions. To study this, we have investigated the transcriptional regulation of theSchizosaccharomyces pombe fbp1 gene that is repressed by a cyclic AMP (cAMP)-dependent protein kinase A (PKA) pathway and is activated by a stress-activated mitogen-activated protein kinase (MAPK) pathway. In this study, we identified and characterized twocis-acting elements in the fbp1 promoter required for activation of fbp1 transcription. Upstream activation site 1 (UAS1), located approximately 900 bp from the transcriptional start site, resembles a cAMP response element (CRE) that is the binding site for the atf1-pcr1 heterodimeric transcriptional activator. Binding of this activator to UAS1 is positively regulated by the MAPK pathway and negatively regulated by PKA. UAS2, located approximately 250 bp from the transcriptional start site, resembles a Saccharomyces cerevisiae stress response element. UAS2 is bound by transcriptional activators and repressors regulated by both the PKA and MAPK pathways, although atf1 itself is not present in these complexes. Transcriptional regulation offbp1 promoter constructs containing only UAS1 or UAS2 confirms that the PKA and MAPK regulation is targeted to both sites. We conclude that the PKA and MAPK signal transduction pathways regulatefbp1 transcription at UAS1 and UAS2, but that the antagonistic interactions between these pathways involve different mechanisms at each site.

scholarly journals Transcriptional Regulation ofFucosyltransferase 1Gene Expression in Colon Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Fumiko Taniuchi ◽  
Koji Higai ◽  
Tomomi Tanaka ◽  
Yutaro Azuma ◽  
Kojiro Matsumoto
Keyword(s):  
Gene Expression ◽  
Colon Cancer ◽  
Transcriptional Regulation ◽  
Binding Site ◽  
Transcriptional Start Site ◽  
Dominant Negative ◽  
Site Directed Mutagenesis ◽  
Luciferase Assay ◽  
Start Site ◽  
Lewis Y

Theα1,2-fucosyltransferase I (FUT1) enzyme is important for the biosynthesis of H antigens, Lewis B, and Lewis Y. In this study, we clarified the transcriptional regulation of FUT1 in the DLD-1 colon cancer cell line, which has high expression of Lewis B and Lewis Y antigens, expresses theFUT1gene, and showsα1,2-fucosyltransferase (FUT) activity. 5′-rapid amplification of cDNA ends revealed a FUT1 transcriptional start site −10 nucleotides upstream of the site registered at NM_000148 in the DataBase of Human Transcription Start Sites (DBTSS). Using the dual luciferase assay,FUT1gene expression was shown to be regulated at the region −91 to −81 nt to the transcriptional start site, which contains the Elk-1 binding site. Site-directed mutagenesis of this region revealed the Elk-1 binding site to be essential for FUT1 transcription. Furthermore, transfection of the dominant negative Elk-1 gene, and the chromatin immunoprecipitation (CHIp) assay, supported Elk-1-dependent transcriptional regulation ofFUT1gene expression in DLD-1 cells. These results suggest that a defined region in the 5′-flanking region of FUT1 is critical for FUT1 transcription and that constitutive gene expression ofFUT1is regulated by Elk-1 in DLD-1 cells.

scholarly journals Identification and transcriptional regulation of the mir-218-1 alternative promoter

2020 ◽  
Author(s):  
Brenna A. Rheinheimer ◽  
Lukas Vrba ◽  
Bernard W Futscher ◽  
Ronald L Heimark
Keyword(s):  
Transcriptional Regulation ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Chromatin Immunoprecipitation ◽  
Transcriptional Start Site ◽  
Regulatory Elements ◽  
Alternative Promoter ◽  
Ductal Adenocarcinoma ◽  
Start Site ◽  
Public Datasets ◽  
Intron 4

AbstractBackgroundmiRNAs are small, endogenous non-coding RNAs approximately 22 nucleotides in length that account for approximately 1% of the genome and play key regulatory roles in multiple signaling pathways. mir-218-1 is an intronic miRNA located within intron 15 of the SLIT2 gene. Public datasets showed enrichment of H3K4me3 within intron 4 of the SLIT2 gene. Therefore, we sought to determine the genomic location and transcriptional regulatory elements of the mir-218-1 candidate alternative promoter in pancreatic ductal adenocarcinoma.MethodsExpression of mir-218 was evaluated in a panel of pancreatic ductal adenocarcinoma cell lines. The mir-218-1 candidate alternative promoter was characterized by chromatin immunoprecipitation, Sequenom, and luciferase assays. Transcriptional regulation of the mir-218-1 candidate alternative promoter was assessed using chromatin immunoprecipitation and an inhibitor to NF-kB.ResultsWe found that expression of mir-218-1 does not correlate with SLIT2 expression and that mir-218-1 has a novel transcriptional start site separate from the SLIT2 promoter. This novel transcriptional start site showed transcriptional activity and was regulated by NF-kB.Conclusionsmir-218-1 is transcribed from an independent and novel transcriptional start site located within intron 4 of the SLIT2 gene in pancreatic ductal adenocarcinoma. Additionally, mir-218-1 expression is regulated by Nf-kB at this alternative transcriptional start site in pancreatic cancer.

scholarly journals Differences in transport function of the human and rat orthologue of the Organic Anion Transporting Polypeptide 2B1 (OATP2B1)

2021 ◽  
pp. 100418
Author(s):  
Janine Hussner ◽  
Annalise Foletti ◽  
Isabell Seibert ◽  
Anja Fuchs ◽  
Eveline Schuler ◽  
...  
Keyword(s):  
Organic Anion ◽  
Transport Function ◽  
Organic Anion Transporting Polypeptide
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