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Mol Cell. 2019 Nov 7;76(3):412-422.e5. doi: 10.1016/j.molcel.2019.08.015. Epub 2019 Sep 12.

RNA Interactions Are Essential for CTCF-Mediated Genome Organization.

Author information

1
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA. Electronic address: ricardo.saldana-meyer@nyulangone.org.
2
Department of Pathology, NYULSoM, New York, NY, USA.
3
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA.
4
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
5
Gladstone Institutes, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA.
6
Gladstone Institutes, San Francisco, CA 94158, USA; Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, USA; Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, USA; Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
7
Department of Pathology, NYULSoM, New York, NY, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA.
8
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, USA; Howard Hughes Medical Institute, NYU Langone Health, New York, NY, USA. Electronic address: danny.reinberg@nyulangone.org.

Abstract

The function of the CCCTC-binding factor (CTCF) in the organization of the genome has become an important area of investigation, but the mechanisms by which CTCF dynamically contributes to genome organization are not clear. We previously discovered that CTCF binds to large numbers of endogenous RNAs, promoting its self-association. In this regard, we now report two independent features that disrupt CTCF association with chromatin: inhibition of transcription and disruption of CTCF-RNA interactions through mutations of 2 of its 11 zinc fingers that are not required for CTCF binding to its cognate DNA site: zinc finger 1 (ZF1) or zinc finger 10 (ZF10). These mutations alter gene expression profiles as CTCF mutants lose their ability to form chromatin loops and thus the ability to insulate chromatin domains and to mediate CTCF long-range genomic interactions. Our results point to the importance of CTCF-mediated RNA interactions as a structural component of genome organization.

KEYWORDS:

CTCF; RNA binding; RNA deficient-mutants; TADs; chromatin domains; chromatin loops; chromatin organization; gene expression; transcriptional inhibition

PMID:
31522988
DOI:
10.1016/j.molcel.2019.08.015
[Indexed for MEDLINE]

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