Chromatin folding below the scale of topologically associating domains (TADs) remains largely unexplored in mammals. Here, we used a high-resolution 3C-based method, Micro-C, to probe links between 3D-genome organization and transcriptional regulation in mouse stem cells. Combinatorial binding of transcription factors, cofactors, and chromatin modifiers spatially segregate TAD regions into microTADs with distinct regulatory features. Enhancer-promoter and promoter-promoter interactions extending from the edge of these domains predominantly link co-regulated loci, often independently of CTCF/Cohesin. Acute inhibition of transcription disrupts the gene-related folding features without altering higher-order chromatin structures. Intriguingly, we detect two-start zig-zag 30-nanometer chromatin fibers. Our work uncovers the finer-scale genome organization that establishes novel functional links between chromatin folding and gene regulation. ONE SENTENCE SUMMARY Transcriptional regulatory elements shape 3D genome architecture of microTADs.
Tsung-Han S. Hsieh • Elena Slobodyanyuk • Anders S. Hansen • Claudia Cattoglio • Oliver J. Rando • Robert Tjian • Xavier Darzacq
May 17th, 2019