Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci.
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.
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Daan
D
Noordermeer
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Marion
M
Leleu
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Department of Molecular Biology, Harvard University, Boston, United States.
Patrick
P
Schorderet
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Elisabeth
E
Joye
Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland.
Fabienne
F
Chabaud
School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Department of Genetics and Evolution, University of Geneva, Geneva, Switzerland denis.duboule@epfl.ch.
Denis
D
Duboule
D000818:Animals; D002451:Cell Compartmentation; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D047108:Embryonic Development / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox; D056426:Genetic Loci; D051379:Mice; D008957:Models, Genetic; D005810:Multigene Family; D018709:Statistics, Nonparametric; D013997:Time Factors; D014158:Transcription, Genetic
D002843:Chromatin
Hox gene regulation; chromatin domains; gene regulation; topological domains