1. Chromosomes and Gene Expression
  2. Developmental Biology

The modular mechanism of chromocenter formation in Drosophila

  1. Madhav Jagannathan  Is a corresponding author
  2. Ryan Cummings
  3. Yukiko M Yamashita  Is a corresponding author
  1. University of Michigan, United States
https://doi.org/10.7554/eLife.43938
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  1. Madhav Jagannathan
  2. Ryan Cummings
  3. Yukiko M Yamashita
(2019)
The modular mechanism of chromocenter formation in Drosophila
eLife 8:e43938.
https://doi.org/10.7554/eLife.43938
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Abstract

A central principle underlying the ubiquity and abundance of pericentromeric satellite DNA repeats in eukaryotes has remained poorly understood. Previously we proposed that the interchromosomal clustering of satellite DNAs into nuclear structures known as chromocenters ensures encapsulation of all chromosomes into a single nucleus (Jagannathan et al., 2018). Chromocenter disruption led to micronuclei formation, resulting in cell death. Here we show that chromocenter formation is mediated by a 'modular' network, where associations between two sequence-specific satellite DNA-binding proteins, D1 and Prod, bound to their cognate satellite DNAs, bring the full complement of chromosomes into the chromocenter. D1 prod double mutants die during embryogenesis, exhibiting enhanced phenotypes associated with chromocenter disruption, revealing the universal importance of satellite DNAs and chromocenters. Taken together, we propose that associations between chromocenter modules, consisting of satellite DNA binding proteins and their cognate satellite DNA, package the Drosophila genome within a single nucleus.

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All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for relevant Figures.

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Author details

  1. Madhav Jagannathan

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    madhavj@umich.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3428-6812

  2. Ryan Cummings

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0540-9174

  3. Yukiko M Yamashita

    Life Sciences Institute, University of Michigan, Ann Arbor, United States
    For correspondence
    yukikomy@umich.edu
    Competing interests
    Yukiko M Yamashita, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5541-0216

Funding

Howard Hughes Medical Institute

  • Yukiko M Yamashita

American Heart Association

  • Madhav Jagannathan

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

© 2019, Jagannathan et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Madhav Jagannathan
  2. Ryan Cummings
  3. Yukiko M Yamashita
(2019)
The modular mechanism of chromocenter formation in Drosophila
eLife 8:e43938.
https://doi.org/10.7554/eLife.43938

Share this article

https://doi.org/10.7554/eLife.43938

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Further reading

    1. Cell Biology
    2. Chromosomes and Gene Expression

    A conserved function for pericentromeric satellite DNA

    Madhav Jagannathan, Ryan Cummings, Yukiko M Yamashita
    Research Article Updated

    A universal and unquestioned characteristic of eukaryotic cells is that the genome is divided into multiple chromosomes and encapsulated in a single nucleus. However, the underlying mechanism to ensure such a configuration is unknown. Here, we provide evidence that pericentromeric satellite DNA, which is often regarded as junk, is a critical constituent of the chromosome, allowing the packaging of all chromosomes into a single nucleus. We show that the multi-AT-hook satellite DNA-binding proteins, Drosophila melanogaster D1 and mouse HMGA1, play an evolutionarily conserved role in bundling pericentromeric satellite DNA from heterologous chromosomes into ‘chromocenters’, a cytological association of pericentromeric heterochromatin. Defective chromocenter formation leads to micronuclei formation due to budding from the interphase nucleus, DNA damage and cell death. We propose that chromocenter and satellite DNA serve a fundamental role in encapsulating the full complement of the genome within a single nucleus, the universal characteristic of eukaryotic cells.