PT  - JOURNAL ARTICLE
AU  - Hsieh, Tsung-Han S.
AU  - Slobodyanyuk, Elena
AU  - Hansen, Anders S.
AU  - Cattoglio, Claudia
AU  - Rando, Oliver J.
AU  - Tjian, Robert
AU  - Darzacq, Xavier
TI  - Resolving the 3D landscape of transcription-linked mammalian chromatin folding
AID  - 10.1101/638775
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 638775
4099  - http://biorxiv.org/content/early/2019/05/17/638775.short
4100  - http://biorxiv.org/content/early/2019/05/17/638775.full
AB  - 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.