Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naive pluripotency.

ABSTRACT: Heterochromatin binding protein HP1β plays an important role in chromatin organization and cell differentiation, however the underlying mechanisms remain unclear. Here, we generated HP1β-/- embryonic stem cells and observed reduced heterochromatin clustering and impaired differentiation. We found that during stem cell differentiation, HP1β is phosphorylated at serine 89 by CK2, which creates a binding site for the pluripotency regulator KAP1. This phosphorylation dependent sequestration of KAP1 in heterochromatin compartments causes a downregulation of pluripotency factors and triggers pluripotency exit. Accordingly, HP1β-/- and phospho-mutant cells exhibited impaired differentiation, while ubiquitination-deficient KAP1-/- cells had the opposite phenotype with enhanced differentiation. The

SUBMITTER: Qin W 

PROVIDER: S-EPMC8287961 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature