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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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 derepression 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.

Original languageEnglish
Article numbere21064
JournaleLife
Volume6
DOIs
Publication statusPublished - Mar 17 2017

Fingerprint

Polycomb Repressive Complex 1
Stem cells
Germ Cells
Fingers
Genes
Cells
Polycomb-Group Proteins
Cell growth
Ablation
Histones
Pluripotent Stem Cells
Mouse Embryonic Stem Cells
Ubiquitination
Transcription Factors
Embryonic Stem Cells
Embryonic Development
Cell Survival

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes. / Endoh, Mitsuhiro; Endo, Takaho A.; Shinga, Jun; Hayashi, Katsuhiko; Farcas, Anca; Ma, Kit Wan; Ito, Shinsuke; Sharif, Jafar; Endoh, Tamie; Onaga, Naoko; Nakayama, Manabu; Ishikura, Tomoyuki; Masui, Osamu; Kessler, Benedikt M.; Suda, Toshio; Ohara, Osamu; Okuda, Akihiko; Klose, Robert; Koseki, Haruhiko.

In: eLife, Vol. 6, e21064, 17.03.2017.

Research output: Contribution to journalArticle

Endoh, M, Endo, TA, Shinga, J, Hayashi, K, Farcas, A, Ma, KW, Ito, S, Sharif, J, Endoh, T, Onaga, N, Nakayama, M, Ishikura, T, Masui, O, Kessler, BM, Suda, T, Ohara, O, Okuda, A, Klose, R & Koseki, H 2017, 'PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes', eLife, vol. 6, e21064. https://doi.org/10.7554/eLife.21064
Endoh, Mitsuhiro ; Endo, Takaho A. ; Shinga, Jun ; Hayashi, Katsuhiko ; Farcas, Anca ; Ma, Kit Wan ; Ito, Shinsuke ; Sharif, Jafar ; Endoh, Tamie ; Onaga, Naoko ; Nakayama, Manabu ; Ishikura, Tomoyuki ; Masui, Osamu ; Kessler, Benedikt M. ; Suda, Toshio ; Ohara, Osamu ; Okuda, Akihiko ; Klose, Robert ; Koseki, Haruhiko. / PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes. In: eLife. 2017 ; Vol. 6.
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