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RNA interactions with CTCF are essential for its proper function

Ricardo Saldaña-Meyer, Javier Rodriguez-Hernaez, Mayilaadumveettil Nishana, Karina Jácome-López, Elphege P. Nora, Benoit G. Bruneau, Mayra Furlan-Magaril, Jane Skok, Danny Reinberg
doi: https://doi.org/10.1101/530014
Ricardo Saldaña-Meyer
1Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA
2Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA
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  • For correspondence: Ricardo.Saldana-Meyer@nyulangone.org Danny.Reinberg@nyulangone.org
Javier Rodriguez-Hernaez
3Department of Pathology, NYULSoM, New York, NY, USA
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Mayilaadumveettil Nishana
3Department of Pathology, NYULSoM, New York, NY, USA
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Karina Jácome-López
4Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Elphege P. Nora
5Gladstone Institutes, San Francisco, CA 94158, USA
6Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA
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Benoit G. Bruneau
5Gladstone Institutes, San Francisco, CA 94158, USA
6Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA
7Department of Pediatrics, University of California, San Francisco, CA 94143, USA
8Cardiovascular Research Institute, University of California, San Francisco, CA 94158, USA
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Mayra Furlan-Magaril
4Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
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Jane Skok
3Department of Pathology, NYULSoM, New York, NY, USA
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Danny Reinberg
1Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA
2Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA
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  • For correspondence: Ricardo.Saldana-Meyer@nyulangone.org Danny.Reinberg@nyulangone.org
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Summary

The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms of how CTCF dynamically contributes to genome organization is not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs; promoting its oligomerization. Here we found that inhibition of transcription or interfering with CTCF ability to bind RNA through mutations of two of its 11 zinc fingers that are not involved with CTCF binding to its cognate site in vitro, zinc finger-1 (ZF1) or −10 (ZF10), disrupt CTCF association to chromatin. These mutations alter gene expression profiles as CTCF mutants lose their ability to promote local insulation. Our results highlight the importance of RNA as a structural component of the genome, in part by affecting the association of CTCF with chromatin and likely its interaction with other factors.

  • Transcriptional inhibition disrupts CTCF binding to chromatin

  • RNA-binding regions (RBR) in CTCF are found within ZF1 and ZF10

  • Local insulation is markedly decreased in ZF1∆ and ZF10∆ mutant rescues

  • Gene expression and chromatin organization are disrupted by RBR mutants

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  • ↵9 Lead Contact

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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. All rights reserved. No reuse allowed without permission.
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Posted January 24, 2019.
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RNA interactions with CTCF are essential for its proper function
Ricardo Saldaña-Meyer, Javier Rodriguez-Hernaez, Mayilaadumveettil Nishana, Karina Jácome-López, Elphege P. Nora, Benoit G. Bruneau, Mayra Furlan-Magaril, Jane Skok, Danny Reinberg
bioRxiv 530014; doi: https://doi.org/10.1101/530014
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RNA interactions with CTCF are essential for its proper function
Ricardo Saldaña-Meyer, Javier Rodriguez-Hernaez, Mayilaadumveettil Nishana, Karina Jácome-López, Elphege P. Nora, Benoit G. Bruneau, Mayra Furlan-Magaril, Jane Skok, Danny Reinberg
bioRxiv 530014; doi: https://doi.org/10.1101/530014

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