Functional and topological characteristics of mammalian regulatory domains (original) (raw)

1. Veli Vural Uslu1,
2. Taro Tsujimura1,
3. Sandra Ruf1,
4. Sonya Nassari1,
5. Wibke Schwarzer1,
6. Laurence Ettwiller2,3 and
7. François Spitz1,4
8. 1Developmental Biology Unit, European Molecular Biology Laboratory, 69117 Heidelberg, Germany;
9. 2Centre for Organismal Studies, University of Heidelberg, 69111 Heidelberg, Germany

• ↵3 Present address: New England Biolabs, Ipswich, MA 01938, USA

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

• ↵4 Corresponding author
  E-mail spitz{at}embl.de

• [Supplemental material is available for this article.]

• 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.

• © 2014 Symmons et al.; Published by Cold Spring Harbor Laboratory Press

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