Ever since the observation that collinearity, that is, the sequential activity of Hox genes based on their relative positions within their gene clusters, is conserved throughout most of the animal kingdom, the question has been raised as to what are the underlying molecular mechanisms. In recent years, technological advances have allowed to uncover changes in chromatin organization that accompany collinearity at Hox gene clusters. Here, we discuss insights in the dynamics of histone modifications and 3D organization in Drosophila and mammals and relate these findings to genomic organization of Hox gene clusters. Using these findings, we propose a framework for collinearity, based on five components: clustering, coating, compaction, compartmentalization, and contacts. We argue that these five components may be sufficient to provide a mechanistic ground for the readout of collinearity in Drosophila and vertebrates.