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
Publication date
2014ISSN
0890-9369
Abstract
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
61 - Medicina
Keywords
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
Pages
13
Publisher
Cold Spring Harbor Laboratory Press
Collection
28;
Is part of
Genes & Development
Citation
Le Dily, Francois; Bau, Davide; Pohl, Andy [et al.]. Distinct structural transitions of chromatin topological domains correlate with coordinated hormone-induced gene regulation. Genes & Development, 2014, 28, p. 2151–2162. Disponible en: <http://genesdev.cshlp.org/content/28/19/2151>. Fecha de acceso: 13 dic. 2021. DOI: 10.1101/gad.241422.114.
Grant agreement number
info:eu-repo/grantAgreement/ES/3PN/BFU2010-19310/BMC
This item appears in the following Collection(s)
- Ciències de la Salut [532]
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/.
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc/4.0/