RT Journal
A1 Andrey, Guillaume
A1 Schöpflin, Robert
A1 Jerković, Ivana
A1 Heinrich, Verena
A1 Ibrahim, Daniel Murad
A1 Paliou, Christina
A1 Hochradel, Myriam
A1 Timmermann, Bernd
A1 Haas, Stefan
A1 Vingron, Martin
A1 Mundlos, Stefan
T1 Characterization of hundreds of regulatory landscapes in developing limbs reveals two regimes of chromatin folding
JF Genome Research 
JO Genome Research 
YR 2016 
FD December 06 
DO 10.1101/gr.213066.116 
SP gr.213066.116 
UL http://genome.cshlp.org/content/early/2016/12/06/gr.213066.116.abstract 
AB Complex regulatory landscapes control the pleiotropic transcriptional activities of developmental genes. For most genes, the number, location and dynamic of their associated regulatory elements are unknown. In this work we characterized the three-dimensional chromatin micro-architecture and regulatory landscape of 446 limb-associated gene loci in mouse using Capture-C, ChIP-seq and RNA-seq in forelimb, hindlimb at three developmental stages and midbrain. The fine mapping of chromatin interactions revealed a strong preference for functional genomic regions such as repressed or active domains. By combining chromatin marks and interaction peaks, we annotated more than one thousand putative limb enhancers and their associated genes. Moreover, the analysis of chromatin interactions revealed two regimes of chromatin folding, one producing interactions stable across tissues and stages and another one associated with tissue and/or stage-specific interactions. Whereas stable interactions associate strongly with CTCF/RAD21 binding, the intensity of variable interactions correlates with changes in underlying chromatin modifications, specifically at the viewpoint and at the interaction site. In conclusion, this comprehensive dataset provides a resource for the characterization of hundreds of limb-associated regulatory landscapes and a framework to interpret the chromatin folding dynamics observed during embryogenesis.