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

被引：331

作者：

Huy Quang Le ^{[1
]}

Ghatak, Sushmita ^{[1
]}

Yeung, Ching-Yan Chloe ^{[1
]}

Tellkamp, Frederik ^{[2
,3
]}

Guenschmann, Christian ^{[2
,3
]}

Dieterich, Christoph ^{[4
]}

Yeroslaviz, Assa ^{[5
]}

Habermand, Bianca ^{[5
]}

Pombo, Ana ^{[6
]}

Niessen, Carien M. ^{[2
,3
]}

Wickstroem, Sara A. ^{[1
,2
]}

机构：

[1] Max Planck Inst Biol Ageing, Paul Gerson Unna Grp Skin Homeostasis & Ageing, D-50931 Cologne, Germany

[2] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany

[3] Univ Cologne, Ctr Mol Med Cologne, Dept Dermatol, D-50931 Cologne, Germany

[4] Max Planck Inst Biol Ageing, Computat RNA Biol & Ageing, D-50931 Cologne, Germany

[5] Max Planck Inst Biochem, Computat Biol, D-82152 Martinsried, Germany

[6] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, D-13092 Berlin, Germany

来源：

NATURE CELL BIOLOGY | 2016年 / 18卷 / 08期

关键词：

INTEGRIN-LINKED KINASE; RNA-POLYMERASE-II; NUCLEAR ACTIN; GENOME-WIDE; CELL-ADHESION; STEM-CELLS; MYOSIN-II; EXPRESSION; CHROMATIN; TISSUE;

D O I：

10.1038/ncb3387

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：864 / +

页数：23

共 58 条

[1] The Histone Demethylase PHF8 Governs Retinoic Acid Response in Acute Promyelocytic Leukemia [J].