TY - JOUR
T1 - Identification and characterization of the human retinoid X receptor alpha gene promoter
AU - Li, Guojun
AU - Yin, Weihong
AU - Chamberlain, Robert
AU - Hewett-Emmett, David
AU - Roberts, Jennifer N.
AU - Yang, Xiulan
AU - Lippman, Scott M.
AU - Clifford, John L.
N1 - Funding Information:
We would like to thank Dr. Miles Wilkinson and members of his laboratory for help with the RNAse protection assays. We thank Drs. David Mentor and Vemparala Subbarayan, along with the other members of the Clinical Cancer Prevention Department laboratories for helpful discussions. We also thank Dr. Lawrence Shimmin (University of Texas Health Sciences Center-Houston, School of Public Health) for valuable technical help and assistance in exploring the genome databases. This work supported in part by NCI 1R29 CA78560 and support for G. Li provided by CA57730 training grant to MD Anderson Cancer Center.
PY - 2006/5/10
Y1 - 2006/5/10
N2 - Retinoid X receptors (RXRs) comprise a family of nuclear retinoid activated transcription factors that are members of the steroid hormone receptor superfamily. RXRs are obligate heterodimerization partners with several other hormone receptor family members, making them critical mediators of a wide range of signaling pathways. Retinoids have been used successfully for the prevention of a number of epithelial cancers, including skin squamous cell carcinoma (SCC). The reduced expression levels of retinoid receptors including RXRα, the predominant RXR expressed in skin, is associated with malignancy in skin SCC. In order to study the regulation of RXRα in skin SCC carcinogenesis we have previously mapped the majority of the human RXRα gene. In the present study we have identified its first exon and promoter region. Exon 1, which contains the translation start site, is located in a highly G + C rich region of the genome at least 58 kb centromeric from exon 2. The promoter region itself is unusually G + C rich (75% G + C in 1200 bp of upstream sequence), has 17 putative SP1 transcription factor binding sites and no TATA or CAAT boxes. Transient transfection experiments with RXRα promoter-luciferase reporter constructs in SRB12-p9 skin SCC cells, as well as with PC3 prostate carcinoma cells, revealed that RXRα transcription is relatively weak compared to the positive control thymidine kinase (TK) promoter and is stimulated by treatment with all-trans retinoic acid (ATRA), the biologically active form of vitamin A. These results indicate that the RXRα gene is transcribed at stable levels, similar to most housekeeping genes, and its transcription is regulated by ATRA. In addition, the 5′ untranslated region of RXRα is highly G + C rich, resulting in a potentially stable folding pattern, that would place RXRα amongst a group of genes that are subject to regulation at the translational level.
AB - Retinoid X receptors (RXRs) comprise a family of nuclear retinoid activated transcription factors that are members of the steroid hormone receptor superfamily. RXRs are obligate heterodimerization partners with several other hormone receptor family members, making them critical mediators of a wide range of signaling pathways. Retinoids have been used successfully for the prevention of a number of epithelial cancers, including skin squamous cell carcinoma (SCC). The reduced expression levels of retinoid receptors including RXRα, the predominant RXR expressed in skin, is associated with malignancy in skin SCC. In order to study the regulation of RXRα in skin SCC carcinogenesis we have previously mapped the majority of the human RXRα gene. In the present study we have identified its first exon and promoter region. Exon 1, which contains the translation start site, is located in a highly G + C rich region of the genome at least 58 kb centromeric from exon 2. The promoter region itself is unusually G + C rich (75% G + C in 1200 bp of upstream sequence), has 17 putative SP1 transcription factor binding sites and no TATA or CAAT boxes. Transient transfection experiments with RXRα promoter-luciferase reporter constructs in SRB12-p9 skin SCC cells, as well as with PC3 prostate carcinoma cells, revealed that RXRα transcription is relatively weak compared to the positive control thymidine kinase (TK) promoter and is stimulated by treatment with all-trans retinoic acid (ATRA), the biologically active form of vitamin A. These results indicate that the RXRα gene is transcribed at stable levels, similar to most housekeeping genes, and its transcription is regulated by ATRA. In addition, the 5′ untranslated region of RXRα is highly G + C rich, resulting in a potentially stable folding pattern, that would place RXRα amongst a group of genes that are subject to regulation at the translational level.
KW - BAC
KW - CpG island
KW - Retinoic acid
KW - Squamous cell carcinoma
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U2 - 10.1016/j.gene.2005.12.027
DO - 10.1016/j.gene.2005.12.027
M3 - Article
C2 - 16517099
AN - SCOPUS:33646048757
SN - 0378-1119
VL - 372
SP - 118
EP - 127
JO - Gene
JF - Gene
IS - 1-2
ER -