RT Journal
A1 Symmons, Orsolya
A1 Uslu, Veli Vural
A1 Tsujimura, Taro
A1 Ruf, Sandra
A1 Nassari, Sonya
A1 Schwarzer, Wibke
A1 Ettwiller, Laurence
A1 Spitz, François
T1 Functional and topological characteristics of mammalian regulatory domains
JF Genome Research 
JO Genome Research 
YR 2014 
FD March 01 
VO 24 
IS 3 
SP 390 
OP 400 
DO 10.1101/gr.163519.113 
UL http://genome.cshlp.org/content/24/3/390.abstract 
AB 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.