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E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family

Author

Listed:
  • Jenny Hsu

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

  • Julia Arand

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

  • Andrea Chaikovsky

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

  • Nancie A. Mooney

    (300 Pasteur Drive, Stanford University)

  • Janos Demeter

    (300 Pasteur Drive, Stanford University)

  • Caileen M. Brison

    (University of California)

  • Romane Oliverio

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

  • Hannes Vogel

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

  • Seth M. Rubin

    (University of California)

  • Peter K. Jackson

    (300 Pasteur Drive, Stanford University)

  • Julien Sage

    (300 Pasteur Drive, Stanford University
    300 Pasteur Drive, Stanford University)

Abstract

E2F transcription factors are central regulators of cell division and cell fate decisions. E2F4 often represents the predominant E2F activity in cells. E2F4 is a transcriptional repressor implicated in cell cycle arrest and whose repressive activity depends on its interaction with members of the RB family. Here we show that E2F4 is important for the proliferation and the survival of mouse embryonic stem cells. In these cells, E2F4 acts in part as a transcriptional activator that promotes the expression of cell cycle genes. This role for E2F4 is independent of the RB family. Furthermore, E2F4 functionally interacts with chromatin regulators associated with gene activation and we observed decreased histone acetylation at the promoters of cell cycle genes and E2F targets upon loss of E2F4 in RB family-mutant cells. Taken together, our findings uncover a non-canonical role for E2F4 that provide insights into the biology of rapidly dividing cells.

Suggested Citation

  • Jenny Hsu & Julia Arand & Andrea Chaikovsky & Nancie A. Mooney & Janos Demeter & Caileen M. Brison & Romane Oliverio & Hannes Vogel & Seth M. Rubin & Peter K. Jackson & Julien Sage, 2019. "E2F4 regulates transcriptional activation in mouse embryonic stem cells independently of the RB family," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10901-x
    DOI: 10.1038/s41467-019-10901-x
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    Cited by:

    1. Mohammad Jaber & Ahmed Radwan & Netanel Loyfer & Mufeed Abdeen & Shulamit Sebban & Areej Khatib & Hazar Yassen & Thorsten Kolb & Marc Zapatka & Kirill Makedonski & Aurelie Ernst & Tommy Kaplan & Yosef, 2022. "Comparative parallel multi-omics analysis during the induction of pluripotent and trophectoderm states," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Brian DeVeale & Leqian Liu & Ryan Boileau & Jennifer Swindlehurst-Chan & Bryan Marsh & Jacob W. Freimer & Adam Abate & Robert Blelloch, 2022. "G1/S restriction point coordinates phasic gene expression and cell differentiation," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Chao-Hui Chang & Feng Liu & Stefania Militi & Svenja Hester & Reshma Nibhani & Siwei Deng & James Dunford & Aniko Rendek & Zahir Soonawalla & Roman Fischer & Udo Oppermann & Siim Pauklin, 2024. "The pRb/RBL2-E2F1/4-GCN5 axis regulates cancer stem cell formation and G0 phase entry/exit by paracrine mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-29, December.
    4. Cheryl A. C. Peretz & Vanessa E. Kennedy & Anushka Walia & Cyrille L. Delley & Andrew Koh & Elaine Tran & Iain C. Clark & Corey E. Hayford & Chris D’Amato & Yi Xue & Kristina M. Fontanez & Aaron A. Ma, 2024. "Multiomic single cell sequencing identifies stemlike nature of mixed phenotype acute leukemia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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