Alternative epigenetic states understood in terms of specific regulatory structures

Generally speaking, epigenetic states or epigenetic regulation refer to situations in which several states of gene expression may coexist in similar environmental conditions, despite the absence of significant changes in the genomic sequence. In one way or another, the mechanisms behind these phenomena involve vicious circles, so that each epigenetic state tends to sustain itself, even after the disappearance of the inductive signal involved in the selection of that particular state. These vicious circles constitute positive feedback circuits and are found at the core of many developmental regulatory systems. In this paper, we present a qualitative model for the regulatory network formed by maternal and gap gene cross-regulations. This network controls the initial anterior-posterior patterning during early Drosophila embryogenesis and encompasses several intertwined feedback circuits. On the basis of our model analysis, we derive interesting insights about how specific expression states of the gap genes are selected along the anterior-posterior axis, in particular in relation with the activity of one positive feedback circuit, namely that formed by giant and Krüppel cross-inhibitions. In addition, we are able to qualitatively simulate the patterns of gene expression in the wild-type, as well as to predict the phenotypes of various loss-of-function mutations at the maternal and gap genes, or cis-regulatory mutations at the gap genes, as well as the effects of ectopic expression of these genes.