Functional and topological characteristics of mammalian regulatory domains
- Orsolya Symmons1,
- Veli Vural Uslu1,
- Taro Tsujimura1,
- Sandra Ruf1,
- Sonya Nassari1,
- Wibke Schwarzer1,
- Laurence Ettwiller2 and
- Francois Spitz1,3
- ↵* Corresponding author; email: spitz{at}embl.de
Abstract
Long-range regulatory interactions have 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 organisation where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles.
- Received July 15, 2013.
- Accepted December 19, 2013.
- Published by Cold Spring Harbor Laboratory Press
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