1. 90 YEARS OF PROGESTERONE: Molecular mechanisms of progesterone receptor action on the breast cancer genome
- Author
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Miguel Beato, François Le Dily, and Roni H. G. Wright
- Subjects
0301 basic medicine ,Mecanismos moleculares ,Gene regulatory network ,Breast Neoplasms ,030209 endocrinology & metabolism ,Context (language use) ,Genomics ,Computational biology ,Biology ,Genome ,Phase Transition ,Càncer de mama ,Progesterone receptor ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Endocrinology ,Cáncer de mama ,Transcriptional regulation ,Humans ,Promoter Regions, Genetic ,Molecular Biology ,Genoma ,Steroid hormones ,Regulation of gene expression ,Genome, Human ,Receptor de progesterona ,Thematic Review ,Molecular mechanisms ,Mecanismes moleculars ,Chromatin Assembly and Disassembly ,Chromatin ,Hormones esteroides ,030104 developmental biology ,Female ,Hormonas esteroides ,Receptors, Progesterone - Abstract
Gene regulation by steroid hormones has been at the forefront in elucidating the intricacies of transcriptional regulation in eukaryotes ever since the discovery by Karlson and Clever that the insect steroid hormone ecdysone induces chromatin puffs in giant chromosomes. After the successful cloning of the hormone receptors toward the end of the past century, detailed mechanistic insight emerged in some model systems, in particular the MMTV provirus. With the arrival of next generation DNA sequencing and the omics techniques, we have gained even further insight into the global cellular response to steroid hormones that in the past decades also extended to the function of the 3D genome topology. More recently, advances in high resolution microcopy, single cell genomics and the new vision of liquid-liquid phase transitions in the context of nuclear space bring us closer than ever to unravelling the logic of gene regulation and its complex integration of global cellular signaling networks. Using the function of progesterone and its cellular receptor in breast cancer cells, we will briefly summarize the history and describe the present extent of our knowledge on how regulatory proteins deal with the chromatin structure to gain access to DNA sequences and interpret the genomic instructions that enable cells to respond selectively to external signals by reshaping their gene regulatory networks. First, the authors thank all the members of the Chromatin and Gene Expression Group, who had performed most of the experiments commented in this review and have made suggestions for the text. The authors also thank their collaborators, most of them cited as authors of the referenced papers. The authors thank the CRG for the continuous support of the group and for the availability of essential core facilities. The experimental work mentioned was supported by the core funding of the CRG, the European Research Council (Project ‘4D Genome’ 609989), the Ministerio de Economía y Competitividad (Project G62426937) and the Generalitat de Catalunya (Project AGAUR SGR 575). We acknowledge support of the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) to the EMBL partnership, the Centro de Excelencia Severo Ochoa as well as CERCA Programme / Generalitat de Catalunya.
- Published
- 2020