MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation

被引：215

作者：

O'Loghlen, Ana ^{[1
,2
]}

Munoz-Cabello, Ana M. ^{[1
,2
]}

Gaspar-Maia, Alexandre ^{[5
]}

Wu, Hsan-Au ^{[5
]}

Banito, Ana ^{[1
,2
]}

Kunowska, Natalia ^{[2
,3
]}

Racek, Tomas ^{[6
]}

Pemberton, Helen N. ^{[6
]}

Beolchi, Patrizia ^{[1
,2
]}

Lavial, Fabrice ^{[7
]}

Masui, Osamu ^{[8
]}

Vermeulen, Michiel ^{[9
,10
]}

Carroll, Thomas ^{[2
]}

Graumann, Johannes ^{[9
,11
]}

Heard, Edith ^{[8
]}

Dillon, Niall ^{[2
,3
]}

Azuara, Veronique ^{[7
]}

Snijders, Ambrosius P. ^{[4
]}

Peters, Gordon ^{[6
]}

Bernstein, Emily ^{[5
]}

Gil, Jesus ^{[1
,2
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Cell Proliferat Grp, London W12 0NN, England

[2] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Epigenet Sect, London W12 0NN, England

[3] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Gene Regulat & Chromatin Grp, London W12 0NN, England

[4] Univ London Imperial Coll Sci Technol & Med, MRC Clin Sci Ctr, Biomol Mass Spectrometry & Prote Lab, London W12 0NN, England

[5] Mt Sinai Sch Med, Dept Oncol Sci, New York, NY 10029 USA

[6] CRUK London Res Inst, Mol Oncol Lab, London WC2A 3PX, England

[7] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London W12 0NN, England

[8] Inst Curie, F-75248 Paris, France

[9] Max Planck Inst Biochem, Dept Prote & Signal Transduct, D-82152 Martinsried, Germany

[10] Univ Med Ctr Utrecht, Dept Mol Canc Res, Utrecht, Netherlands

[11] Qatar Fdn, Weill Cornell Med Coll Qatar, Doha, Qatar

来源：

CELL STEM CELL | 2012年 / 10卷 / 01期

基金：

英国生物技术与生命科学研究理事会;

关键词：

EMBRYONIC STEM-CELLS; METHYLATED HISTONE H3; DEVELOPMENTAL REGULATORS; SKELETAL-MUSCLE; GENES; PLURIPOTENT; SENESCENCE; CIRCUITRY; PROTEINS; INK4A;

D O I：

10.1016/j.stem.2011.12.004

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：

The Polycomb Group (PcG) of chromatin modifiers regulates pluripotency and differentiation. Mammalian genomes encode multiple homologs of the Polycomb repressive complex 1 (PRC1) components, including five orthologs of the Drosophila Polycomb protein (Cbx2, Cbx4, Cbx6, Cbx7, and Cbx8). We have identified Cbx7 as the primary Polycomb ortholog of PRC1 complexes in embryonic stem cells (ESCs). The expression of Cbx7 is downregulated during ESC differentiation, preceding the upregulation of Cbx2, Cbx4, and Cbx8, which are directly repressed by Cbx7. Ectopic expression of Cbx7 inhibits differentiation and X chromosome inactivation and enhances ESC self-renewal. Conversely, Cbx7 knockdown induces differentiation and derepresses lineage-specific markers. In a functional screen, we identified the miR-125 and miR-181 families as regulators of Cbx7 that are induced during ESC differentiation. Ectopic expression of these miRNAs accelerates ESC differentiation via regulation of Cbx7. These observations establish a critical role for Cbx7 and its regulatory miRNAs in determining pluripotency.

引用

页码：33 / 46

页数：14

共 33 条

[1]

Chromatin signatures of pluripotent cell lines [J].