Nanoscale spatial organization of theHoxDgene cluster in distinct transcriptional states

Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation ofHoxdgenes during vertebrate digit development involves modifications in 3D interactions within and around theHoxDgene cluster. This reorganization follows...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2015-11, Vol.112 (45), p.13964-13969
Main Authors: Fabre, Pierre J., Benke, Alexander, Joye, Elisabeth, Huynh, Thi Hanh Nguyen, Manley, Suliana, Duboule, Denis
Format: Article
Language:English
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Summary:Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation ofHoxdgenes during vertebrate digit development involves modifications in 3D interactions within and around theHoxDgene cluster. This reorganization follows a global transition from one set of regulatory contacts to another, between two topologically associating domains (TADs) located on either side of theHoxDlocus. Here, we use 3D DNA FISH to assess the spatial organization of chromatin at and around theHoxDgene cluster and report that although the two TADs are tightly associated, they appear as spatially distinct units. We measured the relative position of genes within the cluster and found that they segregate over long distances, suggesting that a physical elongation of theHoxDcluster can occur. We analyzed this possibility by super-resolution imaging (STORM) and found that tissues with distinct transcriptional activity exhibit differing degrees of elongation. We also observed that the morphological change of theHoxDcluster in developing digits is associated with its position at the boundary between the two TADs. Such variations in the fine-scale architecture of the gene cluster suggest causal links among its spatial configuration, transcriptional activation, and the flanking chromatin context.
ISSN:0027-8424
1091-6490