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An RNA-binding region regulates CTCF clustering and chromatin looping

View ORCID ProfileAnders S. Hansen, View ORCID ProfileTsung-Han S. Hsieh, View ORCID ProfileClaudia Cattoglio, View ORCID ProfileIryna Pustova, View ORCID ProfileXavier Darzacq, View ORCID ProfileRobert Tjian
doi: https://doi.org/10.1101/495432
Anders S. Hansen
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley
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  • ORCID record for Anders S. Hansen
Tsung-Han S. Hsieh
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley
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Claudia Cattoglio
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley
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Iryna Pustova
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley
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Xavier Darzacq
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
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Robert Tjian
1Department of Molecular and Cell Biology, UC Berkeley
2Li Ka Shing Center for Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
3CIRM Center of Excellence, University of California, Berkeley, Berkeley, United States
4Howard Hughes Medical Institute, University of California, Berkeley, Berkeley
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Abstract

Mammalian genomes are folded into Topologically Associating Domains (TADs), consisting of cell-type specific chromatin loops anchored by CTCF and cohesin. Since CTCF and cohesin are expressed ubiquitously, how cell-type specific CTCF-mediated loops are formed poses a paradox. Here we show RNase-sensitive CTCF self-association in vitro and that an RNA-binding region (RBR) mediates CTCF clustering in vivo. Intriguingly, deleting the RBR abolishes or impairs almost half of all chromatin loops in mouse embryonic stem cells. Disrupted loop formation correlates with abrogated clustering and diminished chromatin binding of the RBR mutant CTCF protein, which in turn results in a failure to halt cohesin-mediated extrusion. Thus, CTCF loops fall into at least 2 classes: RBR-independent and RBR-dependent loops. We suggest that evidence for distinct classes of RBR-dependent loops may provide a mechanism for establishing cell-specific CTCF loops regulated by RNAs and other RBR partner.

Footnotes

  • References to computational tools are now included in the main text, instead of just in the Supplementary Methods.

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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 December 16, 2018.
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An RNA-binding region regulates CTCF clustering and chromatin looping
Anders S. Hansen, Tsung-Han S. Hsieh, Claudia Cattoglio, Iryna Pustova, Xavier Darzacq, Robert Tjian
bioRxiv 495432; doi: https://doi.org/10.1101/495432
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An RNA-binding region regulates CTCF clustering and chromatin looping
Anders S. Hansen, Tsung-Han S. Hsieh, Claudia Cattoglio, Iryna Pustova, Xavier Darzacq, Robert Tjian
bioRxiv 495432; doi: https://doi.org/10.1101/495432

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