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Sparse CBX2 nucleates many Polycomb proteins to promote facultative heterochromatinization of Polycomb target genes.
Ingersoll, Steven; Trouth, Abby; Luo, Xinlong; Espinoza, Axel; Wen, Joey; Tucker, Joseph; Astatike, Kalkidan; Phiel, Christopher J; Kutateladze, Tatiana G; Wu, Tao P; Ramachandran, Srinivas; Ren, Xiaojun.
Afiliación
  • Ingersoll S; Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA.
  • Trouth A; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA.
  • Luo X; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Espinoza A; Department of Integrative Biology, University of Colorado Denver, CO 80217-3364, USA.
  • Wen J; Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA.
  • Tucker J; Department of Integrative Biology, University of Colorado Denver, CO 80217-3364, USA.
  • Astatike K; Department of Chemistry, University of Colorado Denver, Denver, CO 80217-3364, USA.
  • Phiel CJ; Department of Integrative Biology, University of Colorado Denver, CO 80217-3364, USA.
  • Kutateladze TG; Department of Pharmacology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
  • Wu TP; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
  • Ramachandran S; Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Aurora, CO, USA.
  • Ren X; RNA Bioscience Initiative, University of Colorado School of Medicine, Aurora, CO, USA.
bioRxiv ; 2024 Feb 05.
Article en En | MEDLINE | ID: mdl-38370615
ABSTRACT
Facultative heterochromatinization of genomic regulators by Polycomb repressive complex (PRC) 1 and 2 is essential in development and differentiation; however, the underlying molecular mechanisms remain obscure. Using genetic engineering, molecular approaches, and live-cell single-molecule imaging, we quantify the number of proteins within condensates formed through liquid-liquid phase separation (LLPS) and find that in mouse embryonic stem cells (mESCs), approximately 3 CBX2 proteins nucleate many PRC1 and PRC2 subunits to form one non-stoichiometric condensate. We demonstrate that sparse CBX2 prevents Polycomb proteins from migrating to constitutive heterochromatin, demarcates the spatial boundaries of facultative heterochromatin, controls the deposition of H3K27me3, regulates transcription, and impacts cellular differentiation. Furthermore, we show that LLPS of CBX2 is required for the demarcation and deposition of H3K27me3 and is essential for cellular differentiation. Our findings uncover new functional roles of LLPS in the formation of facultative heterochromatin and unravel a new mechanism by which low-abundant proteins nucleate many other proteins to form compartments that enable them to execute their functions.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos