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  Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment

Le, H. Q., Ghatak, S., Yeung, C.-Y.-C., Tellkamp, F., Guenschmann, C., Dieterich, C., et al. (2016). Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nature Cell Biology, 18(8), 864-875. doi:10.1038/ncb3387.

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 Urheber:
Le, Huy Quang1, Autor
Ghatak, Sushmita1, Autor
Yeung, Ching-Yan Chloe1, Autor
Tellkamp, Frederik1, Autor
Guenschmann, Christian1, Autor
Dieterich, Christoph1, Autor
Yeroslaviz, Assa2, Autor           
Habermann, Bianca2, Autor           
Pombo, Ana1, Autor
Niessen, Carien M.1, Autor
Wickstroem, Sara A.1, Autor
Affiliations:
1external, ou_persistent22              
2Habermann, Bianca / Computational Biology, Max Planck Institute of Biochemistry, Max Planck Society, ou_1832284              

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Schlagwörter: INTEGRIN-LINKED KINASE; RNA-POLYMERASE-II; NUCLEAR ACTIN; GENOME-WIDE; CELL-ADHESION; STEM-CELLS; MYOSIN-II; EXPRESSION; CHROMATIN; TISSUECell Biology;
 Zusammenfassung: Tissue mechanics drive morphogenesis, but how forces are sensed and transmitted to control stem cell fate and self-organization remains unclear. We show that a mechanosensory complex of emerin (Emd), non-muscle myosin IIA (NMIIA) and actin controls gene silencing and chromatin compaction, thereby regulating lineage commitment. Force-driven enrichment of Emd at the outer nuclear membrane of epidermal stem cells leads to defective heterochromatin anchoring to the nuclear lamina and a switch from H3K9me2,3 to H3K27me3 occupancy at constitutive heterochromatin. Emd enrichment is accompanied by the recruitment of NMIIA to promote local actin polymerization that reduces nuclear actin levels, resulting in attenuation of transcription and subsequent accumulation of H3K27me3 at facultative heterochromatin. Perturbing this mechanosensory pathway by deleting NMIIA in mouse epidermis leads to attenuated H3K27me3-mediated silencing and precocious lineage commitment, abrogating morphogenesis. Our results reveal how mechanics integrate nuclear architecture and chromatin organization to control lineage commitment and tissue morphogenesis.

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Sprache(n): eng - English
 Datum: 2016-07-112016
 Publikationsstatus: Erschienen
 Seiten: 23
 Ort, Verlag, Ausgabe: -
 Inhaltsverzeichnis: -
 Art der Begutachtung: -
 Identifikatoren: ISI: 000380829200007
DOI: 10.1038/ncb3387
 Art des Abschluß: -

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Titel: Nature Cell Biology
  Andere : 'Nat. Cell Biol.'
Genre der Quelle: Zeitschrift
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Ort, Verlag, Ausgabe: London : Macmillan Magazines Ltd.
Seiten: - Band / Heft: 18 (8) Artikelnummer: - Start- / Endseite: 864 - 875 Identifikator: ISSN: 1465-7392
CoNE: https://pure.mpg.de/cone/journals/resource/954925625310