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Elife. 2014 Apr 29;3:e02557. doi: 10.7554/eLife.02557.

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

Author information

  • 1School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • 2School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Department of Molecular Biology, Harvard University, Boston, United States.
  • 3Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland.
  • 4School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland denis.duboule@epfl.ch.

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.DOI: http://dx.doi.org/10.7554/eLife.02557.001.

Copyright © 2014, Noordermeer et al.

KEYWORDS:

Hox gene regulation; chromatin domains; gene regulation; topological domains

PMID:
24843030
[PubMed - in process]
PMCID:
PMC4017647
Free PMC Article
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