Classification of different types of estrogen receptor alpha binding sites in MCF-7 cells

Abstract

Estrogen Receptor alpha (ERα) is a ligand-activated transcription factor and it has a prominent role in both physiological and pathological processes of the reproductive system. ERα has been investigated extensively in breast cancer and the MCF-7 breast-cancer-derived cell line is a widely used model for the study of its behavior. In this paper we provide a systematic catalog of the possible scenarios of binding to more than 80,000 ERα transcription factor binding sites based on the mechanism of ERα binding to DNA (upon both vehicle and estradiol (E2) treatment). A key feature of the estrogen-driven genetic programs is the presence or absence of the specific response element referred to as the estrogen response element (ERE). While ERα-driven super-enhancers are key components of estrogen-dependent genetic programs, three additional classes of enhancers could be identified: one with the presence of ERE where the ERα bound to the DNA prior of E2-treatment, one where the E2 was required for ERα binding even in the presence of ERE, and one where the ERα binding is established through the response elements of the collaborating factors. Our results suggest that different scenarios of ERα binding result in different genetic programs.