TY - JOUR 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 Y1 - 2014/03/01 JF - Genome Research JO - Genome Research SP - 390 EP - 400 DO - 10.1101/gr.163519.113 VL - 24 IS - 3 UR - http://genome.cshlp.org/content/24/3/390.abstract N2 - 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. ER -