Functional and topological characteristics of mammalian regulatory domains
- Orsolya Symmons1,
- Veli Vural Uslu1,
- Taro Tsujimura1,
- Sandra Ruf1,
- Sonya Nassari1,
- Wibke Schwarzer1,
- Laurence Ettwiller2,3 and
- François Spitz1,4
- 1Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;
- 2Centre for Organismal Studies, University of Heidelberg, 69111 Heidelberg, Germany
Abstract
Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles.
Footnotes
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↵4 Corresponding author
E-mail spitz{at}embl.de
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.163519.113.
- Received July 15, 2013.
- Accepted December 19, 2013.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported), as described at http://creativecommons.org/licenses/by-nc/3.0/.
