Functional analysis of differences in transcriptional activity conferred by genetic variants in the 5′ flanking region of the IL12RB2 gene

2015 ◽  
Vol 68 (1) ◽  
pp. 55-65 ◽  
Author(s):  
Nahoko Kato-Kogoe ◽  
Hideki Ohyama ◽  
Soichiro Okano ◽  
Koji Yamanegi ◽  
Naoko Yamada ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Genetic Variants ◽  
Transcriptional Activity ◽  
Flanking Region

scholarly journals Identification and Functional Analysis of a Novel CTNNB1 Mutation in Pediatric Medulloblastoma

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 421
Author(s):  
Lide Alaña ◽  
Caroline E. Nunes-Xavier ◽  
Laura Zaldumbide ◽  
Idoia Martin-Guerrero ◽  
Lorena Mosteiro ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Transcriptional Activity ◽  
Nuclear Accumulation ◽  
Wild Type ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Pediatric Medulloblastoma ◽  
Human Osteosarcoma Cells ◽  
The Central Nervous System ◽  
Ctnnb1 Mutation

Medulloblastoma is the primary malignant tumor of the Central Nervous System (CNS) most common in pediatrics. We present here, the histological, molecular, and functional analysis of a cohort of 88 pediatric medulloblastoma tumor samples. The WNT-activated subgroup comprised 10% of our cohort, and all WNT-activated patients had exon 3 CTNNB1 mutations and were immunostained for nuclear β-catenin. One novel heterozygous CTNNB1 mutation was found, which resulted in the deletion of β-catenin Ser37 residue (ΔS37). The ΔS37 β-catenin variant ectopically expressed in U2OS human osteosarcoma cells displayed higher protein expression levels than wild-type β-catenin, and functional analysis disclosed gain-of-function properties in terms of elevated TCF/LEF transcriptional activity in cells. Our results suggest that the stabilization and nuclear accumulation of ΔS37 β-catenin contributed to early medulloblastoma tumorigenesis.

scholarly journals AT786→C MUTATION IN THE 5’FLANKING REGION OF THE ENDOTHELIAL NITRIC OXIDE GENE REDUCED TRANSCRIPTIONAL ACTIVITY

1997 ◽  
Vol 75 ◽  
pp. 28
Author(s):  
Masafumi Nakayama ◽  
Hirofumi Yasue ◽  
Michihiro Yoshimura ◽  
Yukio Shimasaki ◽  
Kiyotaka Kugiyama ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Transcriptional Activity ◽  
Flanking Region ◽  
Endothelial Nitric Oxide

Functional analysis of genetic variations in the 5′-flanking region of the human MDR1 gene

2011 ◽  
Vol 102 (1) ◽  
pp. 91-98 ◽  
Author(s):  
Mayumi Saeki ◽  
Kouichi Kurose ◽  
Ryuichi Hasegawa ◽  
Masahiro Tohkin
Keyword(s):  
Functional Analysis ◽  
Genetic Variations ◽  
Mdr1 Gene ◽  
Human Mdr1 ◽  
Flanking Region

scholarly journals SNPs identification in swine leptin 5’ flanking region and transcriptional activity of naturally occurring promoter haplotypes

2011 ◽  
Vol 10 (4) ◽  
pp. e49 ◽  
Author(s):  
Alessandra Crisà ◽  
Mariasilvia D’Andrea ◽  
Daniela Willems ◽  
Fabio Pilla ◽  
Alessio Valentini
Keyword(s):  
Transcriptional Activity ◽  
Naturally Occurring ◽  
Flanking Region ◽  
Promoter Haplotypes

scholarly journals Promoter-Specific Repression of Hepatocyte Nuclear Factor (HNF)-1β and HNF-1α Transcriptional Activity by an HNF-1β Missense Mutant Associated with Type 5 Maturity-Onset Diabetes of the Young with Hepatic and Biliary Manifestations

2004 ◽  
Vol 89 (3) ◽  
pp. 1369-1378 ◽  
Author(s):  
Sachiko Kitanaka ◽  
Yuko Miki ◽  
Yasuhide Hayashi ◽  
Takashi Igarashi
Keyword(s):  
Functional Analysis ◽  
Dna Binding ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Dominant Negative ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Onset Diabetes ◽  
Repressive Effect

Abstract Mutations in the hepatocyte nuclear factor (HNF)-1β lead to type 5 maturity-onset diabetes of the young (MODY5). HNF-1β forms a homodimer or a heterodimer with HNF-1α and regulates various target genes. HNF-1β mutations are rare, and no functional analysis has been performed in conjunction with HNF-1α. HNF-1β is expressed in the liver and biliary system and controls liver-specific and bile acid-related genes. Moreover, liver-specific Hnf-1β knockout mice present with severe jaundice. However, no patients with HNF-1β mutations have biliary manifestations. In this report, we found a novel missense mutation in the HNF-1β gene in a patient with neonatal cholestasis and liver dysfunction together with the common features of MODY5. Functional analysis revealed that the mutant HNF-1β had diminished transcriptional activity by loss of the DNA binding activity. The mutant had a promoter-specific dominant-negative transcriptional effect on wild-type HNF-1β and inhibited its DNA binding. Moreover, the mutant had a promoter- and cell-specific transcriptional repressive effect on HNF-1α and a promoter-specific inhibitory effect on HNF-1α DNA binding. From these results, we considered that the different phenotype of patients with HNF-1β mutations might be caused by the different HNF-1β activity in conjunction with the different repression of HNF-1α activity in selected promoters and tissues.

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