Le Dily, FrançoisVidal, EnriqueCuartero, YasminaQuilez Oliete, JavierNacht, A. SilvinaVicent, Guillermo PabloCarbonell-Caballero, JoseSharma, PriyankaVillanueva Cañas, José Luis, 1984-Ferrari, RobertoDe Llobet, Lara IsabelVerde, GaetanoWright, Roni H.G.Beato, Miguel2019-07-042019-07-042019Le Dily F, Vidal E, Cuartero Y, Quilez J, Nacht AS, Vicent GP, Carbonell-Caballero J, Sharma P, Villanueva-Cañas JL, Ferrari R, De Llobet LI, Verde G, Wright RHG, Beato M. Hormone-control regions mediate steroid receptor-dependent genome organization. Genome Res. 2019; 29(1):29-39. DOI 10.1101/gr.243824.1181088-9051http://hdl.handle.net/10230/41930In breast cancer cells, some topologically associating domains (TADs) behave as hormonal gene regulation units, within which gene transcription is coordinately regulated in response to steroid hormones. Here we further describe that responsive TADs contain 20- to 100-kb-long clusters of intermingled estrogen receptor (ESR1) and progesterone receptor (PGR) binding sites, hereafter called hormone-control regions (HCRs). In T47D cells, we identified more than 200 HCRs, which are frequently bound by unliganded ESR1 and PGR. These HCRs establish steady long-distance inter-TAD interactions between them and organize characteristic looping structures with promoters in their TADs even in the absence of hormones in ESR1+-PGR+ cells. This organization is dependent on the expression of the receptors and is further dynamically modulated in response to steroid hormones. HCRs function as platforms that integrate different signals, resulting in some cases in opposite transcriptional responses to estrogens or progestins. Altogether, these results suggest that steroid hormone receptors act not only as hormone-regulated sequence-specific transcription factors but also as local and global genome organizers.application/pdfeng© 2019 Le Dily et al. Published originally by Cold Spring Harbor Laboratory Press at http://dx.doi.org/10.1101/gr.243824.118. Beginning six months from the full-issue publication date, articles are distributed under the Creative Commons Attribution-Non-Commercial 4.0 International License (CC-BY-NC), as described at http://creativecommons.org/licenses/by-nc/4.0/. This license permits non-commercial use, including reproduction, adaptation, and distribution of the article provided the original author and source are credited.Hormone-control regions mediate steroid receptor-dependent genome organizationinfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1101/gr.243824.118info:eu-repo/semantics/openAccess