ArticleNucleic acids research2021
Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency.
Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- HP1γ self-assembles and cooperates with KAP1 in repression of long noncoding RNA AI662270 in ESCs.Cell reports · 2026Article
- Heterochromatome wide analyses reveal MBD2 as a phase separation scaffold for heterochromatin compartmentalization and composition.Nucleic acids research · 2025Article
- The HP1 box of KAP1 organizes HP1α for silencing of endogenous retroviral elements in embryonic stem cells.Nature communications · 2025Article
- Heterochromatic gene silencing controls CD4Nature communications · 2025Article
- Post-translational modifications in the Protein Data Bank.Acta crystallographica. Section D, Structural biology · 2024Review
- The Proteomic Composition and Organization of Constitutive Heterochromatin in Mouse Tissues.Cells · 2024Article
- Heterochromatin organization and phase separation.Nucleus (Austin, Tex.) · 2023Review
- Comprehensive chromatin proteomics resolves functional phases of pluripotency and identifies changes in regulatory components.Nucleic acids research · 2023Article
- The termination of UHRF1-dependent PAF15 ubiquitin signaling is regulated by USP7 and ATAD5.eLife · 2023Article
- NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Probing protein ubiquitination in live cells.Nucleic acids research · 2022Article
- TET1 regulates gene expression and repression of endogenous retroviruses independent of DNA demethylation.Nucleic acids research · 2022Article
- The Putative Bromodomain Protein PfBDP7 of the Human Malaria ParasiteFrontiers in cell and developmental biology · 2022Article
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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. These results suggest that KAP1 regulates pluripotency via its ubiquitination activity. We propose that the formation of subnuclear membraneless heterochromatin compartments may serve as a dynamic reservoir to trap or release cellular factors. The sequestration of essential regulators defines a novel and active role of heterochromatin in gene regulation and represents a dynamic mode of remote control to regulate cellular processes like cell fate decisions.
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