Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

  1. Daan Noordermeer
  2. Marion Leleu
  3. Patrick Schorderet
  4. Elisabeth Joye
  5. Fabienne Chabaud
  6. Denis Duboule  Is a corresponding author
  1. Ecole Polytechnique Fédérale Lausanne, Switzerland
  2. University of Geneva, Switzerland

Abstract

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels.

Article and author information

Author details

  1. Daan Noordermeer

    Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  2. Marion Leleu

    Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Patrick Schorderet

    Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Elisabeth Joye

    Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  5. Fabienne Chabaud

    University of Geneva, Geneva, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Denis Duboule

    Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland
    For correspondence
    denis.duboule@epfl.ch
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Robb Krumlauf, Stowers Institute for Medical Research, United States

Ethics

Animal experimentation: All experiments were performed in agreement with the Swiss law on animal protection (LPA) under license 1008/3482/0 to DD

Version history

  1. Received: February 16, 2014
  2. Accepted: April 7, 2014
  3. Accepted Manuscript published: April 29, 2014 (version 1)
  4. Version of Record published: May 13, 2014 (version 2)

Copyright

© 2014, Noordermeer et al.

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

Metrics

  • 3,589
    views
  • 454
    downloads
  • 120
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Daan Noordermeer
  2. Marion Leleu
  3. Patrick Schorderet
  4. Elisabeth Joye
  5. Fabienne Chabaud
  6. Denis Duboule
(2014)
Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci
eLife 3:e02557.
https://doi.org/10.7554/eLife.02557

Share this article

https://doi.org/10.7554/eLife.02557

Further reading

    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation
    Rajan M Thomas, Matthew C Pahl ... Andrew D Wells
    Research Article

    Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (Ikzf1). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While Ikzf1-Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.

    1. Cell Biology
    2. Chromosomes and Gene Expression
    Lucie Crhak Khaitova, Pavlina Mikulkova ... Karel Riha
    Research Article

    Heat stress is a major threat to global crop production, and understanding its impact on plant fertility is crucial for developing climate-resilient crops. Despite the known negative effects of heat stress on plant reproduction, the underlying molecular mechanisms remain poorly understood. Here, we investigated the impact of elevated temperature on centromere structure and chromosome segregation during meiosis in Arabidopsis thaliana. Consistent with previous studies, heat stress leads to a decline in fertility and micronuclei formation in pollen mother cells. Our results reveal that elevated temperature causes a decrease in the amount of centromeric histone and the kinetochore protein BMF1 at meiotic centromeres with increasing temperature. Furthermore, we show that heat stress increases the duration of meiotic divisions and prolongs the activity of the spindle assembly checkpoint during meiosis I, indicating an impaired efficiency of the kinetochore attachments to spindle microtubules. Our analysis of mutants with reduced levels of centromeric histone suggests that weakened centromeres sensitize plants to elevated temperature, resulting in meiotic defects and reduced fertility even at moderate temperatures. These results indicate that the structure and functionality of meiotic centromeres in Arabidopsis are highly sensitive to heat stress, and suggest that centromeres and kinetochores may represent a critical bottleneck in plant adaptation to increasing temperatures.