Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Heterochromatin drives organization of conventional and inverted nuclei

Martin Falk, View ORCID ProfileYana Feodorova, Natasha Naumova, View ORCID ProfileMaxim Imakaev, View ORCID ProfileBryan R. Lajoie, View ORCID ProfileHeinrich Leonhardt, Boris Joffe, View ORCID ProfileJob Dekker, View ORCID ProfileGeoffrey Fudenberg, View ORCID ProfileIrina Solovei, View ORCID ProfileLeonid Mirny
doi: https://doi.org/10.1101/244038
Martin Falk
1Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yana Feodorova
2Department of Medical Biology, Medical University-Plovdiv, Boulevard Vasil Aprilov 15A, Plovdiv 4000, Bulgaria
5Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yana Feodorova
Natasha Naumova
3Epinomics Inc, 1165A O’Brien Drive, Menlo Park CA 94025
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maxim Imakaev
1Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Maxim Imakaev
Bryan R. Lajoie
4Illumina Incorporated, San Diego, CA 92122, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Bryan R. Lajoie
Heinrich Leonhardt
5Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heinrich Leonhardt
Boris Joffe
5Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Job Dekker
6Howard Hughes Medical Institute, Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA, 01605-0103, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Job Dekker
Geoffrey Fudenberg
7Gladstone Institutes, University of California, San Francisco, CA 94158, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Geoffrey Fudenberg
  • For correspondence: geoff.fudenberg@amail.com irina.solovei@lrz.uni-muenchen.de leonid@mit.edu
Irina Solovei
5Department of Biology II, Center for Integrated Protein Science Munich (CIPSM), Ludwig-Maximilians University Munich, Grosshadernerstrasse 2, 82152 Planegg-Martinsried, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Irina Solovei
  • For correspondence: geoff.fudenberg@amail.com irina.solovei@lrz.uni-muenchen.de leonid@mit.edu
Leonid Mirny
1Institute for Medical Engineering and Science, and Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Leonid Mirny
  • For correspondence: geoff.fudenberg@amail.com irina.solovei@lrz.uni-muenchen.de leonid@mit.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

The mammalian cell nucleus displays a remarkable spatial segregation of active euchromatic from inactive heterochromatic genomic regions. In conventional nuclei, euchromatin is localized in the nuclear interior and heterochromatin at the nuclear periphery. In contrast, rod photoreceptors in nocturnal mammals have inverted nuclei, with a dense heterochromatic core and a thin euchromatic outer shell. This inverted architecture likely converts rod nuclei into microlenses to facilitate nocturnal vision, and may relate to the absence of particular proteins that tether heterochromatin to the lamina. However, both the mechanism of inversion and the role of interactions between different types of chromatin and the lamina in nuclear organization remain unknown. To elucidate this mechanism we performed Hi-C and microscopy on cells with inverted nuclei and their conventional counterparts. Strikingly, despite the inversion evident in microscopy, both types of nuclei display similar Hi-C maps. To resolve this paradox we developed a polymer model of chromosomes and found a universal mechanism that reconciles Hi-C and microscopy for both inverted and conventional nuclei. Based solely on attraction between heterochromatic regions, this mechanism is sufficient to drive phase separation of euchromatin and heterochromatin and faithfully reproduces the 3D organization of inverted nuclei. When interactions between heterochromatin and the lamina are added, the same model recreates the conventional nuclear organization. To further test our models, we eliminated lamina interactions in models of conventional nuclei and found that this triggers a spontaneous process of inversion that qualitatively reproduces the pathway of morphological changes during nuclear inversion in vivo. Together, our experiments and modeling suggest that interactions among heterochromatic regions are central to phase separation of the active and inactive genome in inverted and conventional nuclei, while interactions with the lamina are essential for building the conventional architecture from these segregated phases. Ultimately our data suggest that an inverted organization constitutes the default state of nuclear architecture.

Copyright 
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.
Back to top
PreviousNext
Posted January 09, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Heterochromatin drives organization of conventional and inverted nuclei
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Heterochromatin drives organization of conventional and inverted nuclei
Martin Falk, Yana Feodorova, Natasha Naumova, Maxim Imakaev, Bryan R. Lajoie, Heinrich Leonhardt, Boris Joffe, Job Dekker, Geoffrey Fudenberg, Irina Solovei, Leonid Mirny
bioRxiv 244038; doi: https://doi.org/10.1101/244038
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Heterochromatin drives organization of conventional and inverted nuclei
Martin Falk, Yana Feodorova, Natasha Naumova, Maxim Imakaev, Bryan R. Lajoie, Heinrich Leonhardt, Boris Joffe, Job Dekker, Geoffrey Fudenberg, Irina Solovei, Leonid Mirny
bioRxiv 244038; doi: https://doi.org/10.1101/244038

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Biophysics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4095)
  • Biochemistry (8786)
  • Bioengineering (6493)
  • Bioinformatics (23385)
  • Biophysics (11766)
  • Cancer Biology (9167)
  • Cell Biology (13287)
  • Clinical Trials (138)
  • Developmental Biology (7422)
  • Ecology (11386)
  • Epidemiology (2066)
  • Evolutionary Biology (15118)
  • Genetics (10413)
  • Genomics (14022)
  • Immunology (9145)
  • Microbiology (22108)
  • Molecular Biology (8793)
  • Neuroscience (47435)
  • Paleontology (350)
  • Pathology (1423)
  • Pharmacology and Toxicology (2483)
  • Physiology (3711)
  • Plant Biology (8063)
  • Scientific Communication and Education (1433)
  • Synthetic Biology (2215)
  • Systems Biology (6021)
  • Zoology (1251)