PRC1 Fine-tunes Gene Repression and Activation to Safeguard Skin Development and Stem Cell Specification

被引：100

作者：

Cohen, Idan ^{[1
]}

Zhao, Dejian ^{[2
]}

Bar, Carmit ^{[1
]}

Valdes, Victor J. ^{[1
,10
]}

Dauber-Decker, Katherine L. ^{[1
]}

Minh Binh Nguyen ^{[1
]}

Nakayama, Manabu ^{[3
]}

Rendl, Michael ^{[1
,4
]}

Bickmore, Wendy A. ^{[5
]}

Koseki, Haruhiko ^{[6
,7
]}

Zheng, Deyou ^{[2
,8
,9
]}

Ezhkova, Elena ^{[1
]}

机构：

[1] Icahn Sch Med Mt Sinai, Black Family Stem Cell Inst, Dept Cell Dev & Regenerat Biol, 1 Gustave L Levy Pl, New York, NY 10029 USA

[2] Albert Einstein Coll Med, Dept Genet, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[3] Kazusa DNA Res Inst, Dept Technol Dev, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 2920818, Japan

[4] Icahn Sch Med Mt Sinai, Dept Dermatol, 1 Gustave L Levy Pl, New York, NY 10029 USA

[5] Univ Edinburgh, MRC Inst Genet & Mol Med, MRC Human Genet Unit, Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland

[6] RIKEN Ctr Integrat Med Sci IMS, Lab Dev Genet, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan

[7] Japan Sci & Technol Agcy, CREST, Tsurumi Ku, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan

[8] Albert Einstein Coll Med, Dept Neurol, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[9] Albert Einstein Coll Med, Dept Neurosci, 1300 Morris Pk Ave, Bronx, NY 10461 USA

[10] Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Dept Cell Biol & Dev, Mexico City 04510, DF, Mexico

来源：

CELL STEM CELL | 2018年 / 22卷 / 05期

基金：

英国医学研究理事会;

关键词：

SIGNALING NETWORKS; SELF-RENEWAL; HISTONE H2A; POLYCOMB; PROLIFERATION; PROTEINS; EXPRESSION; RING1B; DIFFERENTIATION; UBIQUITYLATION;

D O I：

10.1016/j.stem.2018.04.005

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

Polycomb repressive complexes (PRCs) 1 and 2 are essential chromatin regulators of cell identity. PRC1, a dominant executer of Polycomb-mediated control, functions as multiple sub-complexes that possess catalytic-dependent H2AK119 mono-ubiquitination (H2AK119ub) and catalytic-independent activities. Here, we show that, despite its well-established repressor functions, PRC1 binds to both silent and active genes. Through in vivo loss-of-function studies, we show that global PRC1 function is essential for skin development and stem cell (SC) specification, whereas PRC1 catalytic activity is dispensable. Further dissection demonstrated that both canonical and non-canonical PRC1 complexes bind to repressed genes, marked by H2AK119ub and PRC2-mediated H3K27me3. Interestingly, loss of canonical PRC1, PRC1 catalytic activity, or PRC2 leads to expansion of mechanosensitive Merkel cells in neonatal skin. Non-canonical PRC1 complexes, however, also bind to and promote expression of genes critical for skin development and SC formation. Together, our findings highlight PRC1's diverse roles in executing a precise developmental program.

引用

页码：726 / +

页数：21

共 61 条

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