A regulatory SNP is a variations which affect the ability of a transcription factor to bind to DNA.

Completion of the human genome project led to the post-genome era. Next important task is to apply differences of genome information of each individual to the personalized medicine. Non-synonymous single nucleotide polymorphisms (SNPs) that result in amino acid changes in proteins were extensively studied. However examples of variation in regulatory sequences are poorly reported, although there are several examples of regulatory SNPs associated with disease susceptibility related to development and differentiation.

As a first step, we focused on retinoid X receptors (RXRs) which are members of the nuclear hormone receptor superfamily and act as ligand-inducible transcription factors. A Ligand of RXR is 9-cis retinoic acid that plays an important role in development, differentiation, and homeostasis. Although RXRs are promiscuous dimerization partners for a lot of nuclear receptors, RXRs also form homodimers whose molecular mechanisms are largely unexplored. To identify RXR homodimer-binding sites in the human genome, we performed a modified yeast one-hybrid system [J Recept Signal Transduct Res. 2010 Apr;30(2):88-105, Methods Mol Biol. 2013;977:125-36] and identified the human genomic fragments with putative RXR homodimer-binding sites. By electrophoresis mobility shift assays, the interaction between human RXR homodimer and the putative binding sites in the obtained genomic fragment. In addition, We identified single nucleotide polymorphisms on the RXR homodimer-binding sites which altered the RXR homodimer-DNA binding affinities. We hope that these results provide insights into the molecular mechanisms underlying the physiological and pathological actions of RXRs. 


 Kazuyuki Yanai

Department of Biomolecular Science, Faculty of Science, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan


  This work was supported by JSPS KAKENHI Grant Number 19681021.