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bioRxiv · 10.1101/003293

Distinct structural transitions of chromatin topological domains coordinate hormone-induced gene regulation

François Le Dily·Davide Baù·Andy Pohl·Guillermo P. Vicent·Daniel Soronellas·Giancarlo Castellano·François Serra·Roni H. G. Wright·Cecilia J. Ballare·Guillaume Filion·Marc A. Marti-Renom·Miguel Beato
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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 described the distribution of Progestin-induced chromatin modifications and changes in transcriptional activity over TADs in T47D breast cancer cells. Using ChIP-Seq, Hi-C and 3D modelling techniques, we found that the borders of the [~]2,000 TADs in these cells are largely maintained after hormone treatment but that some TADs operate as discrete regulatory units in which the majority of the genes are either transcriptionally activated or repressed upon hormone stimulus. The epigenetic signatures of the TADs are coordinately modified by hormone 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. In response to hormone activated TADs exhibit higher density of internal contacts, while repressed TADs show less intra-TAD contacts. Integrative 3D modelling revealed that TADs structurally expanded if activated and compacted when repressed, and that this is accompanied by differential changes in their global accessibility. We thus propose that TADs function as \"regulons\" to enable spatially proximal genes to be coordinately transcribed in response to hormones.

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François Le Dily, Davide Baù, Andy Pohl, Guillermo P. Vicent, Daniel Soronellas, Giancarlo Castellano, François Serra, Roni H. G. Wright, Cecilia J. Ballare, Guillaume Filion, Marc A. Marti-Renom, Miguel Beato. 2014-03-13. Distinct structural transitions of chromatin topological domains coordinate hormone-induced gene regulation. https://doi.org/10.1101/003293

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