PMID: 8945636Nov 1, 1996Paper

RXR-mediated regulation of the alpha-fetoprotein gene through an upstream element

DNA and Cell Biology
C LiY J Wan

Abstract

Retinoic acid (RA) is known to have potent effects on development and differentiation. RA exerts its effects on transcription through two distinct classes of nuclear receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR), that bind to specific RA-responsive elements (RARE) in target genes. alpha-Fetoprotein (AFP), a hepatocyte differentiation, maturation, and carcinogenesis marker, is transcriptionally upregulated by RA in McA-RH8994 hepatoma cells. Using deletion mapping analysis, we have identified a RARE-like sequence that is located between -2406 and -2378 of the transcription initiation site of the rat AFP gene. Sequence analysis demonstrated that this cis-acting element consists of three direct repeats and one inverted repeat of a GGGTCA-like half-site. The putative RARE can specifically bind to both RXR homodimers and RAR/RXR heterodimers as determined by gel mobility shift assays. A DR1 direct repeat was more efficient than a DR5 direct repeat oligonucleotide in competition for binding of the putative RARE to RXR and RAR/RXR. A mutagenesis study indicated that to have a full-strength induction, all the repeats were required. To further analyze the function of this element in vivo, a reporter gene ...Continue Reading

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Citations

Jun 5, 2002·Journal of Hepatology·Saul J Karpen
Oct 2, 2002·Molecular and Cellular Endocrinology·Dong-Ju ShinMary M McGrane
Aug 25, 2001·Biochemical and Biophysical Research Communications·Y OsawaS Nakashima
Jul 1, 2008·Archives of Biochemistry and Biophysics·D C Knutson, M Clagett-Dame
Apr 8, 2003·World Journal of Gastroenterology : WJG·Shao-Ying LuWen-Yong Wang
Feb 14, 2016·Molecular Cancer Therapeutics·Alicia M WatersElizabeth A Beierle
Oct 12, 2000·Biochemical and Biophysical Research Communications·A QianY J Wan

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