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Zafirah Zaidan, SCRMC Trainee, Cell & Regenerative Biology (Sridharan lab)
March 20, 2018 @ 12:00 pm - 1:00 pm
Topic: Compartmentalization of HP1 Proteins in Pluripotency Acquisition and Maintenance
Abstract: Embryonic stem cells (ESCs) have the ability to differentiate into any cell type when exposed to the correct set of stimuli. The chromatin in ESCs is in a decondensed state with lower levels of heterochromatin that is associated with gene repression. Upon ESCs differentiation, large regions of heterochromatin are gained at a global level, leading to a more condensed chromatin state. The Heterochromatin Protein 1 (HP1) family of proteins recognize the repressive histone H3 lysine 9 methylation (H3K9me) and are involved in various functions with maintenance of chromatin structure. During murine somatic cell reprogramming, we find that early depletion of HP1γ 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 HP1γ, indicating the importance of HP1γ release from chromatin for pluripotency acquisition. HP1γ interacted with OCT4 and DPPA4 in HP1α and HP1β knockouts and in H3K9 methylation depleted H3K9M embryonic stem cell (ESC) lines. HP1α and HP1γ 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.