Histone modifications are specifically relocated during gene activation and nuclear differentiation

Background: Post-translational histone modifications (PTMs) and their specific distribution on genes play a crucial role in the control of gene expression, but the regulation of their dynamics upon gene activation and differentiation is still poorly understood. Here, we exploit the unique genome organization of ciliates to analyse PTM dynamics during gene activation in the differentiated cell and during nuclear differentiation. In the macronucleus of these cells the DNA is organized into nanochromosomes which represent independent functional units. Therefore, ciliated protozoa represent a simplistic model system to analyse the relevance of histone modifications and their localization for gene expression and differentiation. Results: We analysed the distribution of three PTMs on six individual nanochromosomes, two of which are silenced in the vegetative cell and only activated during sexual reproduction. We show that a specific relocation of these PTMs correlates with gene activation. Moreover, macronuclear-destined sequences in the differentiating macronucleus display a distribution of PTMs which differs significantly from the PTM patterns of actively transcribed genes. Conclusion: We show for the first time that a relocation of specific histone modifications takes place during activation of genes. In addition, we demonstrate that genes in a differentiating nucleus are characterised by a specific distribution and composition of PTMs. This allows us to propose a mechanistic model about the relevance of PTMs for gene activation, gene silencing and nuclear differentiation. Results described here will be relevant for eukaryotic cells in general.