RT Journal Article SR Electronic T1 High-resolution TADs reveal DNA sequences underlying genome organization in flies JF bioRxiv FD Cold Spring Harbor Laboratory SP 115063 DO 10.1101/115063 A1 Fidel Ramírez A1 Vivek Bhardwaj A1 José Villaveces A1 Laura Arrigoni A1 Björn A. Grüning A1 Kin Chung Lam A1 Bianca Habermann A1 Asifa Akhtar A1 Thomas Manke YR 2017 UL http://biorxiv.org/content/early/2017/03/08/115063.abstract AB Eukaryotic chromatin is partitioned into domains called TADs that are broadly conserved between species and virtually identical among cell types within the same species. Previous studies in mammals have shown that the DNA binding protein CTCF and cohesin contribute to a fraction of TAD boundaries. Apart from this, the molecular mechanisms governing this partitioning remain poorly understood. Using our new software, HiCExplorer, we annotated high-resolution (570 bp) TAD boundaries in flies and identified eight DNA motifs enriched at boundaries. Known insulator proteins bind five of these motifs while the remaining three motifs are novel. We find that boundaries are either at core promoters of active genes or at non-promoter regions of inactive chromatin and that these two groups are characterized by different sets of DNA motifs. Most boundaries are present at divergent promoters of constitutively expressed genes and the gene expression tends to be coordinated within TADs. In contrast to mammals, the CTCF motif is only present on 2% of boundaries in flies. We demonstrate that boundaries can be accurately predicted using only the motif sequences, along with open chromatin, suggesting that DNA sequence encodes the 3D genome architecture in flies. Finally, we present an interactive online database to access and explore the spatial organization of fly, mouse and human genomes, available at http://chorogeome.ie-freiburg.mpg.de.