Visualizing the HoxD Gene Cluster at the Nanoscale Level

Cold Spring Harbor Symposia on Quantitative Biology
Pierre J FabreDenis Duboule

Abstract

Transcription of HoxD cluster genes in limbs is coordinated by two topologically associating domains (TADs), neighboring the cluster and containing various enhancers. Here, we use a combination of microscopy approaches and chromosome conformation capture to assess the structural changes occurring in this global architecture in various functional states. We observed that despite their spatial juxtaposition, the TADs are consistently kept as distinct three-dimensional units. Hox genes located at their boundary can show significant spatial segregation over long distances, suggesting that physical elongation of the HoxD cluster occurs. The use of superresolution imaging (STORM [stochastic optical reconstruction microscopy]) revealed that the gene cluster can be in an either compact or elongated shape. The latter configuration is observed in transcriptionally active tissue and in embryonic stem cells, consistent with chromosome conformation capture results. Such morphological changes at HoxD in developing digits seem to be associated with its position at the boundary between two TADs and support the idea that chromatin dynamics is important in the establishment of transcriptional activity.

References

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Jun 6, 2009·Science·Natalia Soshnikova, Denis Duboule
Jul 28, 2010·Nucleic Acids Research·Maria A FerraiuoloJosée Dostie
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Jul 13, 2011·Nature Reviews. Genetics·Oliver BellDirk Schübeler
Oct 15, 2011·Science·Daan NoordermeerDenis Duboule
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Oct 28, 2015·Proceedings of the National Academy of Sciences of the United States of America·Pierre J FabreDenis Duboule

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Citations

Jun 24, 2017·Current Opinion in Cell Biology·Kelli D Fenelon, Sevan Hopyan
Aug 9, 2017·Genome Biology·Pierre J FabreDenis Duboule
Jun 24, 2017·Biology·Spyros Papageorgiou
Jun 3, 2021·Journal of Developmental Biology·Spyros Papageorgiou
Jul 21, 2021·Journal of the Royal Society, Interface·Phuc NguyenHao Yuan Kueh

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