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

Item Type:Article
Title:Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment
Creators Name:Le, H.Q. and Ghatak, S. and Yeung, C.Y.C. and Tellkamp, F. and Günschmann, C. and Dieterich, C. and Yeroslaviz, A. and Habermann, B. and Pombo, A. and Niessen, C.M. and Wickström, S.A.
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.
Keywords:Cell Differentiation, Cell Lineage, Chromatin, Gene Silencing, Heterochromatin, Histones, Morphogenesis, Nonmuscle Myosin Type IIA, Polycomb-Group Proteins, Protein Binding, Animals, Mice
Source:Nature Cell Biology
Publisher:Nature Publishing Group
Page Range:864-875
Date:August 2016
Official Publication:https://doi.org/10.1038/ncb3387
PubMed:View item in PubMed

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