The genome landscape of ERα- and ERβ-binding DNA regions

In this article, we have applied the ChIP-on-chip approach to pursue a large scale identification of ER alpha- and ER beta-binding DNA regions in intact chromatin. We show that there is a high degree of overlap between the regions identified as bound by ER alpha and ER beta, respectively, but there are also regions that are bound by ER alpha only in the presence of ER beta, as well as regions that are selectively bound by either receptor. Analysis of bound regions shows that regions bound by ER alpha have distinct properties in terms of genome landscape, sequence features, and conservation compared with regions that are bound by ER beta. ER beta-bound regions are, as a group, located more closely to transcription start sites. ER alpha- and ER beta-bound regions differ in sequence properties, with ER alpha-bound regions having an overrepresentation of TA-rich motifs including forkhead binding sites and ER beta-bound regions having a predominance of classical estrogen response elements (EREs) and GC-rich motifs. Differences in the properties of ER bound regions might explain some of the differences in gene expression programs and physiological effects shown by the respective estrogen receptors.