Nanoscale spatial organization of the HoxD gene cluster in distinct transcriptional states.

Abstract:

:Chromatin condensation plays an important role in the regulation of gene expression. Recently, it was shown that the transcriptional activation of Hoxd genes during vertebrate digit development involves modifications in 3D interactions within and around the HoxD gene 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 the HoxD locus. Here, we use 3D DNA FISH to assess the spatial organization of chromatin at and around the HoxD gene 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 the HoxD cluster 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 the HoxD cluster 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.

authors

Fabre PJ,Benke A,Joye E,Nguyen Huynh TH,Manley S,Duboule D

doi

10.1073/pnas.1517972112

subject

Has Abstract

pub_date

2015-11-10 00:00:00

pages

13964-9

issue

45

eissn

0027-8424

issn

1091-6490

pii

1517972112

journal_volume

112

pub_type

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