{Reference Type}: Journal Article
{Title}: Comprehensive study of nuclear receptor DNA binding provides a revised framework for understanding receptor specificity.
{Author}: Penvose A;Keenan JL;Bray D;Ramlall V;Siggers T;
{Journal}: Nat Commun
{Volume}: 10
{Issue}: 1
{Year}: 06 2019 7
{Factor}: 17.694
{DOI}: 10.1038/s41467-019-10264-3
{Abstract}: The type II nuclear receptors (NRs) function as heterodimeric transcription factors with the retinoid X receptor (RXR) to regulate diverse biological processes in response to endogenous ligands and therapeutic drugs. DNA-binding specificity has been proposed as a primary mechanism for NR gene regulatory specificity. Here we use protein-binding microarrays (PBMs) to comprehensively analyze the DNA binding of 12 NR:RXRα dimers. We find more promiscuous NR-DNA binding than has been reported, challenging the view that NR binding specificity is defined by half-site spacing. We show that NRs bind DNA using two distinct modes, explaining widespread NR binding to half-sites in vivo. Finally, we show that the current models of NR specificity better reflect binding-site activity rather than binding-site affinity. Our rich dataset and revised NR binding models provide a framework for understanding NR regulatory specificity and will facilitate more accurate analyses of genomic datasets.