TY  - JOUR
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
Y1  - 2016/12/06 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.213066.116 
SP  - gr.213066.116 
UR  - http://genome.cshlp.org/content/early/2016/12/06/gr.213066.116.abstract 
N2  - 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. 
ER  -