ChIP happens: from biochemical origins to the modern omics toolbox for understanding steroid hormone receptors

Nuclear steroid hormone receptors (SHRs) are ligand-activated transcription factors that mediate cellular responses to steroid hormones (SHs) through regulating gene expression. Understanding the SHR function is crucial for elucidating SH-driven physiology and pathology, including their roles in normal development, metabolism and reproduction, alongside their aberrant function in cancer, endocrine disorders and inflammatory diseases. Investigating the mechanisms that underscore SHR signalling and regulation is therefore essential for advancing our knowledge of both normal physiology and disease and is vital to the development of novel therapeutic strategies. In this review, we examine a range of methods for studying SHR interactions with chromatin and coregulator proteins, from classical biochemical assays to more advanced approaches such as PL-MS, RIME and ChIP. We also highlight potential future innovations in the field, including in situ Calling Cards and UV-induced photocross-linking RIME (UVXL-RIME), that may overcome current methodological limitations, in turn enabling the study of SHRs in increasingly physiologically relevant contexts.