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Visualizing the HoxD Gene Cluster at the Nanoscale Level.

Pierre J Fabre¹, Alexander Benke², Suliana Manley²

¹School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.

Cold Spring Harbor Symposia on Quantitative Biology

|January 16, 2016

Summary

The HoxD gene cluster in developing limbs can change shape from compact to elongated, influencing gene activity. This structural change, linked to its position between two topologically associating domains (TADs), is crucial for transcriptional regulation.

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Area of Science:

Genomics
Developmental Biology
Molecular Biology

Background:

The HoxD gene cluster's transcription in limbs is regulated by neighboring topologically associating domains (TADs) containing enhancers.
Understanding the 3D genome architecture is key to deciphering gene regulation.

Purpose of the Study:

To investigate the structural dynamics of the HoxD cluster and its associated TADs in different functional states.
To correlate chromatin structure with transcriptional activity of HoxD genes.

Main Methods:

Chromosome conformation capture techniques.
Advanced microscopy, including super-resolution imaging (stochastic optical reconstruction microscopy - STORM).

Main Results:

Topologically associating domains (TADs) flanking the HoxD cluster remain distinct structural units.
The HoxD gene cluster exhibits dynamic structural changes, adopting either a compact or elongated conformation.
Elongated conformations are observed in transcriptionally active tissues and embryonic stem cells, correlating with gene activity.

Conclusions:

Chromatin dynamics, particularly the elongation of the HoxD cluster at TAD boundaries, plays a significant role in establishing transcriptional activity.
The spatial organization of the HoxD cluster is intrinsically linked to its regulatory function during development.