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PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

by Farcas, Anca , Okuda, Akihiko , Koseki, Haruhiko , Ito, Shinsuke , Endoh, Tamie , Endoh, Mitsuhiro , Shinga, Jun , Suda, Toshio , Masui, Osamu , Ohara, Osamu , Sharif, Jafar , Kessler, Benedikt M , Ishikura, Tomoyuki , Klose, Robert , Nakayama, Manabu , Ma, Kit-Wan , Onaga, Naoko , Endo, Takaho A , Hayashi, Katsuhiko

in Ablation / Animals / Biology / Cell Biology / Cell Differentiation / Deoxyribonucleic acid / Developmental Biology and Stem Cells / DNA / DNA methylation / Embryo cells / Embryogenesis / Embryonic stem cells / Embryonic Stem Cells - physiology / Epigenetics / Gene expression / Gene Expression Regulation / Gene Silencing / Genes / Genetic aspects / Genomics / germ cells / Histone H2A / Histones - metabolism / Kinases / Laboratories / Medicine / Metalloproteins / Mice / Observations / Physiological aspects / Pluripotency / Polycomb / Polycomb group proteins / Polycomb Repressive Complex 1 - metabolism / Proteins / Stem cell transplantation / Stem cells / Transcription factors / Ubiquitin-Protein Ligases - metabolism / Ubiquitination

2017

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PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

2017

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PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

2017

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Journal Article

PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes

Farcas, Anca,

Okuda, Akihiko,

Koseki, Haruhiko,

Ito, Shinsuke,

Endoh, Tamie,

Endoh, Mitsuhiro,

Shinga, Jun,

Suda, Toshio,

Masui, Osamu,

Ohara, Osamu,

Sharif, Jafar,

Kessler, Benedikt M,

Ishikura, Tomoyuki,

Klose, Robert,

Nakayama, Manabu,

Ma, Kit-Wan,

Onaga, Naoko,

Endo, Takaho A,

Hayashi, Katsuhiko

2017

Overview

The ring finger protein PCGF6 (polycomb group ring finger 6) interacts with RING1A/B and E2F6 associated factors to form a non-canonical PRC1 (polycomb repressive complex 1) known as PCGF6-PRC1. Here, we demonstrate that PCGF6-PRC1 plays a role in repressing a subset of PRC1 target genes by recruiting RING1B and mediating downstream mono-ubiquitination of histone H2A. PCGF6-PRC1 bound loci are highly enriched for promoters of germ cell-related genes in mouse embryonic stem cells (ESCs). Conditional ablation of Pcgf6 in ESCs leads to robust de-repression of such germ cell-related genes, in turn affecting cell growth and viability. We also find a role for PCGF6 in pre- and peri-implantation mouse embryonic development. We further show that a heterodimer of the transcription factors MAX and MGA recruits PCGF6 to target loci. PCGF6 thus links sequence specific target recognition by the MAX/MGA complex to PRC1-dependent transcriptional silencing of germ cell-specific genes in pluripotent stem cells.

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Publisher

eLife Science Publications, Ltd,eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd

Subject

Ablation

/ Animals

/ Biology

/ Cell Biology

/ Cell Differentiation

/ Deoxyribonucleic acid

/ Developmental Biology and Stem Cells