Universität zu Köln

Ghatak, Sushmita, Yeung, Ching-Yan Chloe ORCID: 0000-0002-7076-8109, Tellkamp, Frederik ORCID: 0000-0002-0473-7320, Guenschmann, Christian, Dieterich, Christoph, Yeroslaviz, Assa ORCID: 0000-0001-9638-4026, Habermand, Bianca, Pombo, Ana ORCID: 0000-0002-7493-6288, Niessen, Carien M. and Wickstroem, Sara A. (2016). Mechanical regulation of transcription controls Polycomb-mediated gene silencing during lineage commitment. Nat. Cell Biol., 18 (8). S. 864 - 887. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4679

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ghatak, Sushmita UNSPECIFIED UNSPECIFIED UNSPECIFIED Yeung, Ching-Yan Chloe UNSPECIFIED orcid.org/0000-0002-7076-8109 UNSPECIFIED Tellkamp, Frederik UNSPECIFIED orcid.org/0000-0002-0473-7320 UNSPECIFIED Guenschmann, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Dieterich, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Yeroslaviz, Assa UNSPECIFIED orcid.org/0000-0001-9638-4026 UNSPECIFIED Habermand, Bianca UNSPECIFIED UNSPECIFIED UNSPECIFIED Pombo, Ana UNSPECIFIED orcid.org/0000-0002-7493-6288 UNSPECIFIED Niessen, Carien M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wickstroem, Sara A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-269058
DOI:	10.1038/ncb3387
Journal or Publication Title:	Nat. Cell Biol.
Volume:	18
Number:	8
Page Range:	S. 864 - 887
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-4679
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INTEGRIN-LINKED KINASE; RNA-POLYMERASE-II; NUCLEAR ACTIN; GENOME-WIDE; CELL-ADHESION; STEM-CELLS; MYOSIN-II; EXPRESSION; CHROMATIN; TISSUE Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26905