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bioRxiv · 10.1101/638775

Resolving the 3D landscape of transcription-linked mammalian chromatin folding

Hsieh, T.-H. S.·Slobodyanyuk, E.·Hansen, A. S.·Cattoglio, C.·Rando, O. J.·Tjian, R.·Darzacq, X.
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Abstract

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.\n\nONE SENTENCE SUMMARYTranscriptional regulatory elements shape 3D genome architecture of microTADs.

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Hsieh, T.-H. S., Slobodyanyuk, E., Hansen, A. S., Cattoglio, C., Rando, O. J., Tjian, R., Darzacq, X.. 2019-05-17. Resolving the 3D landscape of transcription-linked mammalian chromatin folding. https://doi.org/10.1101/638775

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