1. Chromosomes and Gene Expression
Download icon

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
Research Article
  • Cited 71
  • Views 3,285
  • Annotations
Cite this article as: eLife 2014;3:e02557 doi: 10.7554/eLife.02557

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.

Ethics

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

Reviewing Editor

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

Publication 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

  • 3,285
    Page views
  • 383
    Downloads
  • 71
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

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)

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

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

Categories and tags

Research organism

Further reading

    1. Chromosomes and Gene Expression

    Checkpoint inhibition of origin firing prevents inappropriate replication outside of S-phase

    Mark C Johnson et al.
    Research Article Updated

    Checkpoints maintain the order of cell cycle events during DNA damage or incomplete replication. How the checkpoint response is tailored to different phases of the cell cycle remains poorly understood. The S-phase checkpoint for example results in the slowing of replication, which in budding yeast occurs by Rad53-dependent inhibition of the initiation factors Sld3 and Dbf4. Despite this, we show here that Rad53 phosphorylates both of these substrates throughout the cell cycle at the same sites as in S-phase, suggesting roles for this pathway beyond S-phase. Indeed, we show that Rad53-dependent inhibition of Sld3 and Dbf4 limits re-replication in G2/M, preventing gene amplification. In addition, we show that inhibition of Sld3 and Dbf4 in G1 prevents premature initiation at all origins at the G1/S transition. This study redefines the scope of the ‘S-phase checkpoint’ with implications for understanding checkpoint function in cancers that lack cell cycle controls.

    1. Chromosomes and Gene Expression
    2. Neuroscience

    A transcriptomic taxonomy of Drosophila circadian neurons around the clock

    Dingbang Ma et al.
    Research Article

    Many different functions are regulated by circadian rhythms, including those orchestrated by discrete clock neurons within animal brains. To comprehensively characterize and assign cell identity to the 75 pairs of Drosophila circadian neurons, we optimized a single cell RNA sequencing method and assayed clock neuron gene expression at different times of day. The data identify at least 17 clock neuron categories with striking spatial regulation of gene expression. Transcription factor regulation is prominent and likely contributes to the robust circadian oscillation of many transcripts, including those that encode cell-surface proteins previously shown to be important for cell recognition and synapse formation during development. The many other clock-regulated genes also constitute an important resource for future mechanistic and functional studies between clock neurons and/or for temporal signaling to circuits elsewhere in the fly brain.

    1. Chromosomes and Gene Expression
    2. Physics of Living Systems

    The interplay between asymmetric and symmetric DNA loop extrusion

    Edward J Banigan, Leonid A Mirny
    Research Advance Updated

    Chromosome compaction is essential for reliable transmission of genetic information. Experiments suggest that ∼1000-fold compaction is driven by condensin complexes that extrude chromatin loops, by progressively collecting chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates that symmetric two-sided loop extrusion can achieve such compaction, but recent single-molecule studies (Golfier et al., 2020) observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, and asymmetric two-sided extrusion. We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.