scholarly journals A distal activation domain is critical in the regulation of the rat androgen receptor gene promoter

1993 ◽  
Vol 294 (3) ◽  
pp. 779-784 ◽  
Author(s):  
C S Song ◽  
S Her ◽  
M Slomczynska ◽  
S J Choi ◽  
M H Jung ◽  
...  

The far upstream region of the rat androgen receptor (AR) gene has been cloned, and the nucleotide sequence up to -2656 bp established. Nested deletion mutants of rat AR 5′ flanking sequences were ligated to the luciferase reporter gene, and their promoter activities were examined in transfected COS1 cells. Results show a critical cis-acting domain located between positions -960 and -940. Deletion of this cis element resulted in a greater than 90% decrease in the promoter activity. A nuclear protein that specifically binds to this 21-nucleotide sequence was identified by gel mobility shift analysis. The -960/-940 cis element has no identify to the binding sequence of any known transcription factor. Furthermore, the cognate binding protein is present in both rat and human (HeLa) cell nuclear extracts. We conclude that a novel trans-activator interacting at the -960/-940 region plays a critical role in the regulation of AR gene expression.

1998 ◽  
Vol 275 (4) ◽  
pp. G778-G788 ◽  
Author(s):  
Martín G. Martín ◽  
Jiafang Wang ◽  
Tony W. H. Li ◽  
Jason T. Lam ◽  
Edgar M. Gutierrez ◽  
...  

The regulatory elements that control basal and activated transcriptional expression of the polymeric IgA receptor gene ( pIgR) have not been defined. In this study, we performed functional analysis of the murine pIgR 5′-upstream region. Transient transfection studies identified the gene’s minimal promoter to reside within 110 nucleotides upstream from the start of transcription. Substitution mutations of this region identified both a putative activator (−78 to −70) and a repressor (−66 to −52) element. DNase I footprint analysis confirmed an area of protection that spans from nucleotides −85 to −62. Mobility shift assays of the putative region confirmed binding of upstream stimulatory factor 1 (USF1) to an E box element at positions −75 and −70, representing the putative enhancer. Overexpression studies using various forms of USF suggest that both USF1 and USF2 enhance activity of the pIgR minimal promoter. We report the identification and characterization of the murine pIgR minimal promoter, as well as the critical role of USF in enhancing its basal level of transcription in Caco-2 cells.


Endocrinology ◽  
2004 ◽  
Vol 145 (2) ◽  
pp. 781-789 ◽  
Author(s):  
Liying Zhang ◽  
Martin Charron ◽  
William W. Wright ◽  
Bandana Chatterjee ◽  
Chung S. Song ◽  
...  

Abstract The androgen receptor (AR) in Sertoli cells mediates the actions of testosterone on spermatogenesis. However, the transcription factors responsible for AR gene regulation in Sertoli cells remain unknown. In this study, we determined that nuclear factor-κB (NF-κB) regulates transcription of AR in primary cultures of Sertoli cells isolated from testes of adult rats. Electrophoretic mobility shift and antibody supershift assays with nuclear extracts prepared from Sertoli cells identified two binding sites, termed κB1 at −491/−482 bp and κB2 at −574/−565 bp, upstream of the transcription start site of the AR gene that bind the NF-κB subunits, p50 and p65. DNAse I footprint analyses showed that binding of the p50 NF-κB subunit protected the same regions on the rat AR promoter. Analyses of AR promoter-luciferase reporter gene activity after transfection of primary cultures of Sertoli cells demonstrated that mutation of the κB2 site or combined mutation of the κB1 and κB2 sites reduced activity by 40%. Preferential binding of the transcriptionally active p65/p50 heterodimer to the κB2 site rather than to the κB1 site supported these observations. Overexpression of the NF-κB p65 and p50 subunits in Sertoli cells increased activity from the wild-type AR promoter and the promoter with mutation of the κB1 site, but not the κB2 site. Activity was further stimulated by CBP (CREB binding protein), a coactivator of p65 transcriptional activity. Taken together, our data show that NF-κB is an activator of AR gene transcription in Sertoli cells and may be an important determinant of androgen activity during spermatogenesis.


2006 ◽  
Vol 175 (4S) ◽  
pp. 136-136
Author(s):  
Ralph Buttyan ◽  
Xuezhen Yang ◽  
Min-Wei Chen ◽  
Debra L. Bemis ◽  
Mitchell C. Benson ◽  
...  

2019 ◽  
Vol 13 (3) ◽  
pp. 205-222 ◽  
Author(s):  
Gabriel L. Schlomer ◽  
Jessica Murray ◽  
Brianna Yates ◽  
Kerry Hair ◽  
David J. Vandenbergh

1990 ◽  
Vol 265 (15) ◽  
pp. 8893-8900 ◽  
Author(s):  
W G Yarbrough ◽  
V E Quarmby ◽  
J A Simental ◽  
D R Joseph ◽  
M Sar ◽  
...  

1999 ◽  
Vol 162 (1) ◽  
pp. 269-270
Author(s):  
E. Giovannucci ◽  
E.A. Platz ◽  
M.J. Stampfer ◽  
A. Chan ◽  
K. Krithivas ◽  
...  

2021 ◽  
Author(s):  
Anna Cremonini ◽  
Luca Saragoni ◽  
Luca Morandi ◽  
Angelo G. Corradini ◽  
Caterina Ravaioli ◽  
...  

AbstractCarcinomas with apocrine differentiation (CAD) of the breast are rare tumours typically presenting high immunohistochemical expression of androgen receptor (AR) which is a target molecule for personalised therapy. To date, no studies have evaluated the genetic changes that are associated with AR immunohistochemical expression in CADs. The present work aims to characterise AR status in CADs. Twenty CAD tumours were studied with immunohistochemistry, in situ fluorescence hybridization and DNA methylation analysis, to evaluate AR expression and its regulator status. All tumours demonstrated high AR immunohistochemical expression, with over 95% of the neoplastic cells showing AR positivity in 19/20 cases. CADs showed AR gene copy loss in a percentage of neoplastic cells ranging from 5 to 84% (mean 48.93%). AR regulator genes, including the MAGE family, UXT and FLNA, presented variable methylation levels, but were mainly hypomethylated and therefore all transcriptionally active. The results of this study indicate that CADs present AR monosomy, paralleled by higher transcriptional activity of the gene with potential to influence response to AR deprivation therapy.


Sign in / Sign up

Export Citation Format

Share Document