The chromatin source-sink hypothesis: a shared mode of chromatin-mediated regulations

We propose that several chromatin-mediated regulatory processes are dominated by source-sink relationships in which factors operate as ‘sources’ to produce or provide a resource and compete with each other to occupy separate ‘sinks’. In this model, large portions of genomic DNA operate as ‘sinks’, which are filled by ‘sources’, such as available histone variants, covalent modifications to histones, the readers of these modifications and non-coding RNAs. Competing occupation for the sinks by different sources leads to distinct states of genomic equilibrium in differentiated cells. During dynamic developmental events, such as sexual reproduction, we propose that dramatic and rapid reconfiguration of source-sink relationships modifies chromatin states. We envision that re-routing of sources could occur by altering the dimensions of the sink, by reconfiguration of existing sink occupation or by varying the size of the source, providing a central mechanism to explain a plethora of epigenetic phenomena, which contribute to phenotypic variegation, zygotic genome activation and nucleolar dominance.