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

Le HQ, Ghatak S, Yeung CY, Tellkamp F, Günschmann C, Dieterich C, Yeroslaviz A, Habermann B, Pombo A, Niessen CM, Wickström SA

Nat. Cell Biol. 2016 Aug;18(8):864-75

PMID: 27398909

Abstract

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.

  • News

  • Upcoming Events

    There are no upcoming events at this time.

  • December 2020
    M T W T F S S
     123456
    78910111213
    14151617181920
    21222324252627
    28293031  

© 2017 SFB 829

Durch die weitere Nutzung der Seite stimmst du der Verwendung von Cookies zu. Weitere Informationen

Die Cookie-Einstellungen auf dieser Website sind auf "Cookies zulassen" eingestellt, um das beste Surferlebnis zu ermöglichen. Wenn du diese Website ohne Änderung der Cookie-Einstellungen verwendest oder auf "Akzeptieren" klickst, erklärst du sich damit einverstanden.

Schließen