Physical forces cause HoxD gene cluster elongation
4th International Congress on Drug Discovery, Designing and Development & International Conference and Exhibition on Biochemistry, Molecular Biology: R&D
November 02-03, 2017 Chicago, USA
National Center for Scientific Research-Demokritos, Greece
Scientific Tracks Abstracts : J Pharmacol Ther Res
Hox gene collinearity is a fundamental property in the process of Hox gene expression. It correlates the 3’ to 5’ sequential gene alignment in the Hox gene cluster with the ontogenetic units along the anterior/posterior axis of the embryo. This property is multiscalar and cannot be treated by biomolecular mechanisms alone. In multiscale phenomena physical laws must come into play. The biophysical model (BM) provides the necessary tools for an integrated multiscalar explanation of Hox collinearity. According to BM, physical forces are created which pull the Hox genes sequentially from the compact inactive Hox gene cluster toward the transcription factory domain, where gene transcription is possible. The BM successfully describes the genetic engineering experiments where some genes of the vertebrate Hox cluster are deleted (or duplicated). Although the BM was introduced in 2001, it is only in the last 2 years that it has been adopted by the scientific community, because the evidence was missing for the existence of such forces. However, recent instrumental progress in achieving high imaging resolution (e.g. 3D DNA FISH, STORM etc.) make possible the confirmation of several BM predictions. For instance, it is found that the mouse HoxD cluster is elongated up to 5-6 times during Hox gene transcription. These unexpected physical deformations agree with the BM predictions. New experiments are proposed to test further the biophysical model. A synthesis of Biophysics and Biochemistry is proposed to explain Hox gene collinearity in two steps: in a first step, the BM forces translocate the Hox genes in the right location for transcription. In a second step, biomolecular mechanisms transcribe the translocated genes.
Spyros Papageorgiou has graduated in Physics from the Athens University, Greece. He has received his DPhil in Theoretical Physics from Oxford and Sussex Universities in 1965. He was a Research Fellow at Theory Division of CERN 1968-1970 and a Corresponding Fellow between CERN and Demokritos, Greece 1970-1973. In 1976, he started working on models in Developmental Biology. He formulated models in reaction-diffusion, pattern regulation, regeneration, gene expression etc. In 2000, he became Emeritus Research Director at ‘Demokritos’ and he currently study the Hox gene collinearity problem. He formulated the biophysical model (BM) (S Papageorgiou, BIOLOGY 2017,6, 32) based on the hypothesis of physical forces translocating the Hox genes toward the transcription factory domain where transcription is possible.