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Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency

Author

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  • Emma Bell

    (Imperial College London, Hammersmith Hospital)

  • Edward W. Curry

    (Imperial College London, Hammersmith Hospital)

  • Wout Megchelenbrink

    (Radboud University, Faculty of Science, Department of Molecular Biology
    Princess Máxima Center for Pediatric Oncology
    University of Campania Luigi Vanvitelli)

  • Luc Jouneau

    (Université Paris-Saclay, INRAE, ENVA, BREED, Domaine de Vilvert, bat 230)

  • Vincent Brochard

    (Université Paris-Saclay, INRAE, ENVA, BREED, Domaine de Vilvert, bat 230)

  • Rute A. Tomaz

    (Imperial College London, Hammersmith Hospital)

  • King Hang T. Mau

    (Imperial College London, Hammersmith Hospital)

  • Yaser Atlasi

    (Radboud University, Faculty of Science, Department of Molecular Biology)

  • Roshni A. de Souza

    (Imperial College London, Hammersmith Hospital)

  • Hendrik Marks

    (Radboud University, Faculty of Science, Department of Molecular Biology)

  • Hendrik G. Stunnenberg

    (Radboud University, Faculty of Science, Department of Molecular Biology
    Princess Máxima Center for Pediatric Oncology)

  • Alice Jouneau

    (Université Paris-Saclay, INRAE, ENVA, BREED, Domaine de Vilvert, bat 230)

  • Véronique Azuara

    (Imperial College London, Hammersmith Hospital)

Abstract

Clusters of enhancers, referred as to super-enhancers (SEs), control the expression of cell identity genes. The organisation of these clusters, and how they are remodelled upon developmental transitions remain poorly understood. Here, we report the existence of two types of enhancer units within SEs typified by distinctive CpG methylation dynamics in embryonic stem cells (ESCs). We find that these units are either prone for decommissioning or remain constitutively active in epiblast stem cells (EpiSCs), as further established in the peri-implantation epiblast in vivo. Mechanistically, we show a pivotal role for ESRRB in regulating the activity of ESC-specific enhancer units and propose that the developmentally regulated silencing of ESRRB triggers the selective inactivation of these units within SEs. Our study provides insights into the molecular events that follow the loss of ESRRB binding, and offers a mechanism by which the naive pluripotency transcriptional programme can be partially reset upon embryo implantation.

Suggested Citation

  • Emma Bell & Edward W. Curry & Wout Megchelenbrink & Luc Jouneau & Vincent Brochard & Rute A. Tomaz & King Hang T. Mau & Yaser Atlasi & Roshni A. de Souza & Hendrik Marks & Hendrik G. Stunnenberg & Ali, 2020. "Dynamic CpG methylation delineates subregions within super-enhancers selectively decommissioned at the exit from naive pluripotency," Nature Communications, Nature, vol. 11(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14916-7
    DOI: 10.1038/s41467-020-14916-7
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    Cited by:

    1. Woranop Sukparangsi & Elena Morganti & Molly Lowndes & Hélène Mayeur & Melanie Weisser & Fella Hammachi & Hanna Peradziryi & Fabian Roske & Jurriaan Hölzenspies & Alessandra Livigni & Benoit Gilbert G, 2022. "Evolutionary origin of vertebrate OCT4/POU5 functions in supporting pluripotency," Nature Communications, Nature, vol. 13(1), pages 1-21, December.
    2. Andrea Lauria & Guohua Meng & Valentina Proserpio & Stefania Rapelli & Mara Maldotti & Isabelle Laurence Polignano & Francesca Anselmi & Danny Incarnato & Anna Krepelova & Daniela Donna & Chiara Levra, 2023. "DNMT3B supports meso-endoderm differentiation from mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

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