Clarifying the biological nature of the interaction between the systems-based epigenetic landscape and the epigenome

The epigenetic landscape concept initially proposed by Conrad H. Waddington has become a powerful tool to quantitatively address constraints underlying cell differentiation and morphogenesis. In theoretical and experimental terms, this has been enabled by grounding gene regulatory network models on experimental data. Such models have, in turn, led to proposing epigenetic landscape models that entail functional and structural constraints of cell differentiation and morphogenetic dynamics, and thus the understanding of development from a systems–based perspective. Therefore, it is mainly in the context of the study of development where the epigenetic landscape has been anchored as a conceptual support. On the other hand, nonetheless, given the recent understanding of gene control by epigenomic modifications and the capacity to profile these modifications using high– throughput molecular techniques, the notion of epigenetics has been mainly related to non-genetic heritable modifications of the genome. Therefore, this approach, which until now has not been based on a systems–based dynamical treatment, has given proximal epigenomic modifications a central role in understanding development. The latter, has left the dynamic view of epigenetic landscape aside. In this paper we aim at establishing a conceptual link between both conceptualizations of epigenetic regulation.