Physical Forces May Cause the HoxD Gene Cluster Elongation

Hox gene collinearity was discovered be Edward B. Lewis in 1978. It consists of the Hox1, Hox2, Hox3 ordering of the Hox genes in the chromosome from the telomeric to the centromeric side of the chromosome. Surprisingly, the spatial activation of the Hox genes in the ontogenetic units of the embryo follows the same ordering along the anterior-posterior embryonic axis. The chromosome microscale differs from the embryo macroscale by 3 to 4 orders of magnitude. The traditional biomolecular mechanisms are not adequate to comprise phenomena at so divergent spatial domains. A Biophysical Model of physical forces was proposed which can bridge the intermediate space and explain the results of genetic engineering experiments. Recent progress in constructing instruments and achieving high resolution imaging (e.g., 3D DNA FISH, STORM etc.) enable the assessment of the geometric structure of the chromatin during the different phases of Hox gene activation. It is found that the mouse HoxD gene cluster is elongated up to 5-6 times during Hox gene transcription. These unexpected findings agree with the BM predictions. It is now possible to measure several physical quantities inside the nucleus during Hox gene activation. New experiments are proposed to test further this model.