TITLE:
Identification and Characterization of Human Genomic Binding Sites for Retinoic Acid Receptor/Retinoid X Receptor Heterodimers
AUTHORS:
Kenta Hosoda, Masashi Sato, Kazuyuki Yanai
KEYWORDS:
All-Trans Retinoic Acid, Retinoic Acid Receptor, Retinoid X Receptor, Yeast One-Hybrid System, Polymorphism, Regulatory SNP
JOURNAL NAME:
Advances in Biological Chemistry,
Vol.5 No.2,
March
23,
2015
ABSTRACT: All-trans retinoic acid (ATRA) triggers a wide range of effects on vertebrate development by regulating cell proliferation, differentiation, and apoptosis. ATRA activates retinoic acid receptors (RARs) which heterodimerize with retinoid X receptors (RXRs). RAR/RXR heterodimers function as ATRA-dependent transcriptional regulators by binding to retinoic acid response elements (RAREs). To identify RAR/RXR heterodimer-binding sites in the human genome, we performed a modified yeast one-hybrid assays and identified 193 RAR/RXR heterodimer-binding fragments in the human genome. The putative target genes included genes involved in development process and cell differentiation. Gel mobility shift assays indicated that 160 putative RAREs could directly interact with the RAR/RXR heterodimer. Moreover, 19 functional regulatory single nucleotide polymorphisms (rSNPs) on the RAR/RXR-binding sequences were identified by analyzing the difference in the DNA-binding affinities. These results provide insights into the molecular mechanisms underlying the physiological and pathological actions of RAR/RXR heterodimers.