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

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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.

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Daan Noordermeer

Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Marion Leleu

Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Patrick Schorderet

Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland

Competing interests
The authors declare that no competing interests exist.
Elisabeth Joye

Ecole Polytechnique Fédérale Lausanne, Lausanne, Switzerland

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The authors declare that no competing interests exist.
Fabienne Chabaud

University of Geneva, Geneva, Switzerland

Competing interests
The authors declare that no competing interests exist.
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

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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.