Phasing the intranuclear organization of steroid hormone receptors

STORTZ, MARTIN; PRESMAN, DIEGO M.; PECCI, ADALI; LEVI, VALERIA

BIOCHEMICAL JOURNAL

PORTLAND PRESS LTD

Año: 2021 vol. 478 p. 443 - 461

0264-6021

Steroid receptors (SRs) encompass a family of transcription factors that regulate theexpression of thousands of genes upon binding to steroid hormones and include theglucocorticoid, androgen, progesterone, estrogen and mineralocorticoid receptors. SRscontrol key physiological and pathological processes, thus becoming relevant drugtargets. As with many other nuclear proteins, hormone-activated SRs concentrate in multiplediscrete foci within the cell nucleus. Even though these foci were first observed ∼25years ago, their exact structure and function remained elusive. In the last years, newimaging methodologies and theoretical frameworks improved our understanding of theintranuclear organization. These studies led to a new paradigm stating that many membranelessnuclear compartments, including transcription-related foci, form through aliquid?liquid phase separation process. These exciting ideas impacted the SR field byraising the hypothesis of SR foci as liquid condensates involved in transcriptional regulation.In this work, we review the current knowledge about SR foci formation under thelight of the condensate model, analyzing how these structures may impact SR function.These new ideas, combined with state-of-the-art techniques, may shed light on the biophysicalmechanisms governing the formation of SR foci and the biological function ofthese structures in normal physiology and disease