RNA Interactions Are Essential for CTCF-Mediated Genome Organization
Por:
Saldaña-Meyer R., Rodriguez-Hernaez, Javier, Escobar, Thelma, Nishana, Mayilaadumveettil, Jacome-Lopez, Karina, Nora, Elphege P., Bruneau, Benoit G., Tsirigos, Aristotelis, Furlan-Magaril, Mayra, Skok, Jane, Reinberg, Danny
Publicada:
1 ene 2019
Resumen:
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. © 2019 Elsevier Inc.RNA binding promotes CTCF-dependent chromatin loops. Saldaña-Meyer et al. show that mutation of the RNA-binding regions in CTCF (ZF1 and ZF10) disrupts gene expression, chromatin binding, and the formation of chromatin loops. © 2019 Elsevier Inc.
Filiaciones:
Saldaña-Meyer R.:
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, United States
Howard Hughes Medical Institute, NYU Langone Health, New York, NY, United States
Rodriguez-Hernaez, Javier:
Department of Pathology, NYULSoM, New York, NY, United States
NYULSoM, Dept Pathol, New York, NY USA
Escobar, Thelma:
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, United States
Howard Hughes Medical Institute, NYU Langone Health, New York, NY, United States
NYULSoM, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA
NYU Langone Hlth, Howard Hughes Med Inst, New York, NY 10016 USA
Nishana, Mayilaadumveettil:
Department of Pathology, NYULSoM, New York, NY, United States
NYULSoM, Dept Pathol, New York, NY USA
Jacome-Lopez, Karina:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Genet Mol, Mexico City, DF, Mexico
Nora, Elphege P.:
Gladstone Institutes, San Francisco, CA 94158, United States
Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, United States
Gladstone Inst, San Francisco, CA 94158 USA
Roddenberry Ctr Stem Cell Biol & Med Gladstone, San Francisco, CA 94158 USA
Bruneau, Benoit G.:
Gladstone Institutes, San Francisco, CA 94158, United States
Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, San Francisco, CA 94158, United States
Department of Pediatrics, University of California, San Francisco, San Francisco, CA 94143, United States
Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94158, United States
Gladstone Inst, San Francisco, CA 94158 USA
Roddenberry Ctr Stem Cell Biol & Med Gladstone, San Francisco, CA 94158 USA
Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA
Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94158 USA
Tsirigos, Aristotelis:
Department of Pathology, NYULSoM, New York, NY, United States
Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, United States
NYULSoM, Dept Pathol, New York, NY USA
NYU, Sch Med, Appl Bioinformat Labs, New York, NY 10016 USA
Furlan-Magaril, Mayra:
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Genet Mol, Mexico City, DF, Mexico
Skok, Jane:
Department of Pathology, NYULSoM, New York, NY, United States
NYULSoM, Dept Pathol, New York, NY USA
Reinberg, Danny:
Department of Biochemistry and Molecular Pharmacology, NYULSoM, New York, NY, United States
Howard Hughes Medical Institute, NYU Langone Health, New York, NY, United States
NYULSoM, Dept Biochem & Mol Pharmacol, New York, NY 10016 USA
NYU Langone Hlth, Howard Hughes Med Inst, New York, NY 10016 USA
|