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Two independent modes of chromatin organization revealed by cohesin removal

Author

Listed:
  • Wibke Schwarzer

    (Developmental Biology Unit. European Molecular Biology Laboratory)

  • Nezar Abdennur

    (Computational and Systems Biology Program, Massachusetts Institute of Technology)

  • Anton Goloborodko

    (Massachusetts Institute of Technology)

  • Aleksandra Pekowska

    (Genome Biology Unit. European Molecular Biology Laboratory)

  • Geoffrey Fudenberg

    (Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology)

  • Yann Loe-Mie

    (Institut Pasteur, (Epi)genomics of Animal Development Unit
    CNRS, UMR3738)

  • Nuno A Fonseca

    (European Bioinformatics Institute. European Molecular Biology Laboratory. Wellcome Trust Genome Campus)

  • Wolfgang Huber

    (Genome Biology Unit. European Molecular Biology Laboratory)

  • Christian H. Haering

    (Cell Biology and Biophysics Unit, European Molecular Biology Laboratory)

  • Leonid Mirny

    (Massachusetts Institute of Technology
    Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology)

  • Francois Spitz

    (Developmental Biology Unit. European Molecular Biology Laboratory
    Genome Biology Unit. European Molecular Biology Laboratory
    Institut Pasteur, (Epi)genomics of Animal Development Unit
    CNRS, UMR3738)

Abstract

Imaging and chromosome conformation capture studies have revealed several layers of chromosome organization, including segregation into megabase-sized active and inactive compartments, and partitioning into sub-megabase domains (TADs). It remains unclear, however, how these layers of organization form, interact with one another and influence genome function. Here we show that deletion of the cohesin-loading factor Nipbl in mouse liver leads to a marked reorganization of chromosomal folding. TADs and associated Hi-C peaks vanish globally, even in the absence of transcriptional changes. By contrast, compartmental segregation is preserved and even reinforced. Strikingly, the disappearance of TADs unmasks a finer compartment structure that accurately reflects the underlying epigenetic landscape. These observations demonstrate that the three-dimensional organization of the genome results from the interplay of two independent mechanisms: cohesin-independent segregation of the genome into fine-scale compartments, defined by chromatin state; and cohesin-dependent formation of TADs, possibly by loop extrusion, which helps to guide distant enhancers to their target genes.

Suggested Citation

  • Wibke Schwarzer & Nezar Abdennur & Anton Goloborodko & Aleksandra Pekowska & Geoffrey Fudenberg & Yann Loe-Mie & Nuno A Fonseca & Wolfgang Huber & Christian H. Haering & Leonid Mirny & Francois Spitz, 2017. "Two independent modes of chromatin organization revealed by cohesin removal," Nature, Nature, vol. 551(7678), pages 51-56, November.
  • Handle: RePEc:nat:nature:v:551:y:2017:i:7678:d:10.1038_nature24281
    DOI: 10.1038/nature24281
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