RT Journal Article
SR Electronic
T1 Resolving the 3D landscape of transcription-linked mammalian chromatin folding
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 638775
DO 10.1101/638775
A1 Hsieh, Tsung-Han S.
A1 Slobodyanyuk, Elena
A1 Hansen, Anders S.
A1 Cattoglio, Claudia
A1 Rando, Oliver J.
A1 Tjian, Robert
A1 Darzacq, Xavier
YR 2019
UL http://biorxiv.org/content/early/2019/05/17/638775.abstract
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.