Identification and Characterization of Human Genomic Binding Sites for Retinoic Acid Receptor/Retinoid X Receptor Heterodimers
Year: 2015
Type: article
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.
Source: Advances in Biological Chemistry
Authors: Kenta Hosoda, Masashi Sato, Kazuyuki Yanai
Institution: Toho University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W2063105977