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Int. J. Mol. Sci. 2018, 19(2), 306;

Signaling by Steroid Hormones in the 3D Nuclear Space

Gene Regulation, Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology (BIST), Doctor Aiguader 88, 08003 Barcelona, Spain
Universitat Pompeu Fabra (UPF), 08003 Barcelona, Spain
Author to whom correspondence should be addressed.
Received: 29 December 2017 / Revised: 18 January 2018 / Accepted: 19 January 2018 / Published: 23 January 2018
(This article belongs to the Special Issue Molecular Pathways of Estrogen Receptor Action)
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Initial studies showed that ligand-activated hormone receptors act by binding to the proximal promoters of individual target genes. Genome-wide studies have now revealed that regulation of transcription by steroid hormones mainly depends on binding of the receptors to distal regulatory elements. Those distal elements, either enhancers or silencers, act on the regulation of target genes by chromatin looping to the gene promoters. In the nucleus, this level of chromatin folding is integrated within dynamic higher orders of genome structures, which are organized in a non-random fashion. Terminally differentiated cells exhibit a tissue-specific three-dimensional (3D) organization of the genome that favors or restrains the activity of transcription factors and modulates the function of steroid hormone receptors, which are transiently activated upon hormone exposure. Conversely, integration of the hormones signal may require modifications of the 3D organization to allow appropriate transcriptional outcomes. In this review, we summarize the main levels of organization of the genome, review how they can modulate the response to steroids in a cell specific manner and discuss the role of receptors in shaping and rewiring the structure in response to hormone. Taking into account the dynamics of 3D genome organization will contribute to a better understanding of the pleiotropic effects of steroid hormones in normal and cancer cells. View Full-Text
Keywords: chromatin conformation; estrogen receptor; steroid receptors; topological domains; transcription regulation chromatin conformation; estrogen receptor; steroid receptors; topological domains; transcription regulation

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Le Dily, F.; Beato, M. Signaling by Steroid Hormones in the 3D Nuclear Space. Int. J. Mol. Sci. 2018, 19, 306.

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