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

View ORCID ProfileTsung-Han S. Hsieh, View ORCID ProfileElena Slobodyanyuk, View ORCID ProfileAnders S. Hansen, View ORCID ProfileClaudia Cattoglio, View ORCID ProfileOliver J. Rando, View ORCID ProfileRobert Tjian, View ORCID ProfileXavier Darzacq
doi: https://doi.org/10.1101/638775
Tsung-Han S. Hsieh
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
4Center for Computational Biology, University of California, Berkeley, Berkeley, United States
5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
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  • ORCID record for Tsung-Han S. Hsieh
Elena Slobodyanyuk
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
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  • ORCID record for Elena Slobodyanyuk
Anders S. Hansen
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
6Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, United States
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Claudia Cattoglio
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
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Oliver J. Rando
7Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA, United States
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  • ORCID record for Oliver J. Rando
Robert Tjian
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
5Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States
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  • For correspondence: darzacq@berkeley.edu jmlim@berkeley.edu
Xavier Darzacq
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences
3CIRM Center of Excellence
4Center for Computational Biology, University of California, Berkeley, Berkeley, United States
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  • ORCID record for Xavier Darzacq
  • For correspondence: darzacq@berkeley.edu jmlim@berkeley.edu
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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.

ONE SENTENCE SUMMARY Transcriptional regulatory elements shape 3D genome architecture of microTADs.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 17, 2019.
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Resolving the 3D landscape of transcription-linked mammalian chromatin folding
Tsung-Han S. Hsieh, Elena Slobodyanyuk, Anders S. Hansen, Claudia Cattoglio, Oliver J. Rando, Robert Tjian, Xavier Darzacq
bioRxiv 638775; doi: https://doi.org/10.1101/638775
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Resolving the 3D landscape of transcription-linked mammalian chromatin folding
Tsung-Han S. Hsieh, Elena Slobodyanyuk, Anders S. Hansen, Claudia Cattoglio, Oliver J. Rando, Robert Tjian, Xavier Darzacq
bioRxiv 638775; doi: https://doi.org/10.1101/638775

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