دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Phosphorylation of the HP1β hinge region sequesters KAP1 in heterochromatin and promotes the exit from naïve pluripotency.
المؤلفون: Qin W; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany., Ugur E; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany.; Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany., Mulholland CB; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany., Bultmann S; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany., Solovei I; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany., Modic M; The Francis Crick Institute and UCL Queen Square Institute of Neurology, London NW1 1AT, United Kingdom., Smets M; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany., Wierer M; Department of Proteomics and Signal Transduction, Max Planck Institute for Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany., Forné I; Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Planegg-Martinsried, Germany., Imhof A; Biomedical Center Munich, Faculty of Medicine, Ludwig-Maximilians-Universität München, Großhaderner Str. 9, 82152 Planegg-Martinsried, Germany., Cardoso MC; Cell Biology and Epigenetics, Department of Biology, Technical University of Darmstadt, 64287 Darmstadt, Germany., Leonhardt H; Faculty of Biology, Ludwig-Maximilians-Universität München, Butenandtstraße 1, D-81377 Munich, Germany.
المصدر: Nucleic acids research [Nucleic Acids Res] 2021 Jul 21; Vol. 49 (13), pp. 7406-7423.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 0411011 Publication Model: Print Cited Medium: Internet ISSN: 1362-4962 (Electronic) Linking ISSN: 03051048 NLM ISO Abbreviation: Nucleic Acids Res Subsets: MEDLINE
أسماء مطبوعة: Publication: 1992- : Oxford : Oxford University Press
Original Publication: London, Information Retrieval ltd.
مواضيع طبية MeSH: Chromosomal Proteins, Non-Histone/*metabolism , Embryonic Stem Cells/*metabolism , Heterochromatin/*metabolism , Tripartite Motif-Containing Protein 28/*metabolism, Animals ; Casein Kinase II/metabolism ; Cell Differentiation ; Cell Line ; Cells, Cultured ; Chromobox Protein Homolog 5 ; Chromosomal Proteins, Non-Histone/chemistry ; Chromosomal Proteins, Non-Histone/genetics ; Chromosomal Proteins, Non-Histone/physiology ; Cricetinae ; Embryonic Stem Cells/cytology ; Gene Knockout Techniques ; Humans ; Mice ; Phosphorylation ; Serine/metabolism ; Tripartite Motif-Containing Protein 28/genetics ; Tripartite Motif-Containing Protein 28/physiology
مستخلص: 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.
(© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)
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المشرفين على المادة: 0 (CBX1 protein, human)
0 (Cbx1 protein, mouse)
0 (Chromosomal Proteins, Non-Histone)
0 (Heterochromatin)
107283-02-3 (Chromobox Protein Homolog 5)
452VLY9402 (Serine)
EC 2.3.2.27 (TRIM28 protein, human)
EC 2.3.2.27 (Trim28 protein, mouse)
EC 2.3.2.27 (Tripartite Motif-Containing Protein 28)
EC 2.7.11.1 (Casein Kinase II)
تواريخ الأحداث: Date Created: 20210702 Date Completed: 20210809 Latest Revision: 20211204
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC8287961
DOI: 10.1093/nar/gkab548
PMID: 34214177
قاعدة البيانات: MEDLINE
الوصف
تدمد:1362-4962
DOI:10.1093/nar/gkab548