Towards Resolving the Enigma of HOX Gene Collinearity

Abstract

The development of normal patterns along the primary and secondary vertebrate axes depends on the regularity of the early HOX gene expressions. During the initial developmental stages these expressions form a sequential pattern of partially overlapping domains along the anterior-posterior axis of the embryo in coincidence with the 3′ to 5′ order of the genes in the chromosome (spatial collinearity). In addition, the HOX genes are activated one after the other in the same 3′ to 5′ order (temporal collinearity). Genetic engineering experiments were performed in order explore the mechanism responsible for these remarkable collinearity phenomena. Several biomolecular models were proposed explaining some of the experimental findings. A biophysical model has been also proposed which is based on the hypothesis that physical forces are created which act on the Hox cluster. This cluster is initially inactive, located inside the chromosome territory. The physical forces translocate sequentially the Hox genes one after the other from inside the chromosome territory towards the interchromosome domain where they are activated in the area of the transcription factories. The above biophysical model mechanism has been strongly supported by recent experimental evidence and some evolutionary considerations. In this model realization, pulling forces are created between the ‘negatively’ charged Hox cluster and its ‘positively’ charged chromatin environment.