Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance

The heterochromatin protein 1 (HP1) family is involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1 gamma reduces the generation of induced pluripotent stem cells, while late depletion enhances the process, with a concomitant change from a centromeric to nucleoplasmic localization and elongation-associated histone H3.3 enrichment. Depletion of heterochromatin anchoring protein SENP7 increased reprogramming efficiency to a similar extent as HP1g, indicating the importance of HP1g release from chromatin for pluripotency acquisition. HP1g interacted with OCT4 and DPPA4 in HP1 alpha and HP1 beta knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1 alpha and HP1g complexes in ESCs differed in association with histones, the histone chaperone CAF1 complex, and specific components of chromatin-modifying complexes such as DPY30, implying distinct functional contributions. Taken together, our results reveal the complex contribution of the HP1 proteins to pluripotency.