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Mitotic bookmarking redundancy by nuclear receptors in pluripotent cells.
Chervova, Almira; Molliex, Amandine; Baymaz, H Irem; Coux, Rémi-Xavier; Papadopoulou, Thaleia; Mueller, Florian; Hercul, Eslande; Fournier, David; Dubois, Agnès; Gaiani, Nicolas; Beli, Petra; Festuccia, Nicola; Navarro, Pablo.
Afiliação
  • Chervova A; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
  • Molliex A; Equipe Labéllisée Ligue Contre le cancer, Paris, France.
  • Baymaz HI; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
  • Coux RX; Equipe Labéllisée Ligue Contre le cancer, Paris, France.
  • Papadopoulou T; Institute of Molecular Biology, Mainz, Germany.
  • Mueller F; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
  • Hercul E; Equipe Labéllisée Ligue Contre le cancer, Paris, France.
  • Fournier D; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
  • Dubois A; Equipe Labéllisée Ligue Contre le cancer, Paris, France.
  • Gaiani N; Department of Computational Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3691, Imaging and Modeling Unit, Paris, France.
  • Beli P; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
  • Festuccia N; Equipe Labéllisée Ligue Contre le cancer, Paris, France.
  • Navarro P; Department of Developmental and Stem Cell Biology, Institut Pasteur, Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells Unit, Paris, France.
Nat Struct Mol Biol ; 31(3): 513-522, 2024 Mar.
Article em En | MEDLINE | ID: mdl-38196033
ABSTRACT
Mitotic bookmarking transcription factors (TFs) are thought to mediate rapid and accurate reactivation after mitotic gene silencing. However, the loss of individual bookmarking TFs often leads to the deregulation of only a small proportion of their mitotic targets, raising doubts on the biological significance and importance of their bookmarking function. Here we used targeted proteomics of the mitotic bookmarking TF ESRRB, an orphan nuclear receptor, to discover a large redundancy in mitotic binding among members of the protein super-family of nuclear receptors. Focusing on the nuclear receptor NR5A2, which together with ESRRB is essential in maintaining pluripotency in mouse embryonic stem cells, we demonstrate conjoint bookmarking activity of both factors on promoters and enhancers of a large fraction of active genes, particularly those most efficiently reactivated in G1. Upon fast and simultaneous degradation of both factors during mitotic exit, hundreds of mitotic targets of ESRRB/NR5A2, including key players of the pluripotency network, display attenuated transcriptional reactivation. We propose that redundancy in mitotic bookmarking TFs, especially nuclear receptors, confers robustness to the reestablishment of gene regulatory networks after mitosis.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Cromatina Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Fatores de Transcrição / Cromatina Limite: Animals Idioma: En Ano de publicação: 2024 Tipo de documento: Article