For over 50 years, steroid hormone receptors have been a premiere model system for investigating mechanisms of gene regulation. Steroid hormones such as oestrogens and cortisol are released from endocrine glands into the circulation where they can access cells throughout the body. These hormones can pass through the cell membrane to bind their cognate nuclear receptors, which are transcription factors. Ligand-bound receptors undergo conformational changes to facilitate binding both to DNA and to co-factors that facilitate interactions with chromatin and core transcriptional machinery to activate or repress gene expression. This ligand-dependent change in receptor function provides an ideal experimental switch with which to characterize hormone-dependent gene programmes that modulate central aspects of mammalian physiology such as metabolism, stress response and puberty, as well as the growth and metastasis of some cancers.

One transformative advance in the study of steroid receptors was a 2006 publication from Carroll et al., which reported a comprehensive map of where ligand-bound oestrogen receptor-α (ERα) is recruited to the genome of the MCF-7 breast cancer cell line. The authors used chromatin immunoprecipitation (ChIP) and the then recently available Affymetrix Human tiling 1.0 microarrays to profile the occupancy of both ERα and RNA polymerase II within the entirety of the non-repetitive human genome. This ‘ChIP-on-chip’ approach itself was not new, having been previously published in several contexts including the yeast genome, human promoter arrays and the entirety of human chromosomes 21 and 22. However, this first ‘genome-wide’ description of transcription factor binding in mammalian cells clarified fundamental principles of steroid receptor action and provided a proof-of-principle for future profiling of transcription factor binding in diverse species and biological contexts.