Fig. 7

Working model depicting a role for HP1γ R38 and R39 during stem cell differentiation. In pluripotent stem cells, HP1γ proteins bound to specific genomic loci (e.g. Nanog promoter) are citrullinated (cit) by PADI4 to reduce their affinity to chromatin, whilst the diffusion of soluble HP1γ molecules is not affected. This may explain, at least in part, how a relatively open chromatin conformation at specific gene loci and potentially expression of pluripotency genes in stem cells is maintained. A similar (non-mutually exclusive) mechanism was identified for H1 [22], which interacts with HP1γ in stem cells with reduced pluripotent potential [39]. Upon differentiation, PADI4 expression decreases and the subsequent reduction in HP1γ citrullination would promote its interaction with chromatin (increased specific residence time) which may result in chromatin compaction and/or changes in gene expression