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Title:	Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation
Author:	Le Dily, François; Bau, Davide; Pohl, Andy; Vicent, Guillermo P.; Serra, Francois; Soronellas, Daniel; Castellano, Giancarlo; Wright, Roni H.G.; Ballare, Cecilia; Filion, Guillaume; Marti-Renom, Marc A.; Beato, Miguel
Notes:	The human genome is segmented into topologically associating domains (TADs), but the role of this conserved organization during transient changes in gene expression is not known. Here we describe the distribution of progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-seq (chromatin immunoprecipitation combined with high-throughput sequencing), Hi-C (chromosome capture followed by high-throughput sequencing), and three-dimensional (3D) modeling techniques, we found that the borders of the ∼2000 TADs in these cells are largely maintained after hormone treatment and that up to 20% of the TADs could be considered as discrete regulatory units where the majority of the genes are either transcriptionally activated or repressed in a coordinated fashion. The epigenetic signatures of the TADs are homogeneously modified by hormones in correlation with the transcriptional changes. Hormone-induced changes in gene activity and chromatin remodeling are accompanied by differential structural changes for activated and repressed TADs, as reflected by specific and opposite changes in the strength of intra-TAD interactions within responsive TADs. Indeed, 3D modeling of the Hi-C data suggested that the structure of TADs was modified upon treatment. The differential responses of TADs to progestins and estrogens suggest that TADs could function as “regulons” to enable spatially proximal genes to be coordinately transcribed in response to hormones.
Subject(s):	-Estructura tridimensional del genoma -Expressió gènica -Regulació transcripcional -Paisatge epigenètic -Receptor de progesterona -Estructura tridimensional del genoma -Expresión genética -Regulación transcripcional -Paisaje epigenético -Receptor de progesterona -Three-dimensional structure of the genome -Genetic expression -Transcriptional regulation -Epigenetic landscape -Progesterone receptor -61
Rights:	© 2014 Le Dily et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. http://creativecommons.org/licenses/by-nc/4.0/
Document type:	Article Article - Published version
Published by:	Cold Spring Harbor Laboratory Press
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