Europe PMC

This website requires cookies, and the limited processing of your personal data in order to function. By using the site you are agreeing to this as outlined in our privacy notice and cookie policy.

LINE1 and PRC2 control nucleolar organization and repression of the 8C state in human ESCs.

Author information

Affiliations

  • 1. Lunenfeld-Tanenbaum Research Institute and Department of Molecular Genetics, University of Toronto, Toronto, ON M5T 3H7, Canada.
      Authors
    • Zhang J 1
    • Ataei L 1
    • Mittal K 1
    • Caldwell L 1
    • Tse K 1
    • Cook DP 1
    • Trcka D 1
    • Wrana JL 1
    • Ramalho-Santos M 1
    (9 authors)
  • 2. Laboratory of Integrative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China.
      Authors
    • Wu L 2
    • Mazid MA 2
    (2 authors)
  • 3. Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2M9, Canada.
      Authors
    • Huynh L 3
    (1 author)
  • 4. Department of Biological Sciences, University of Toronto Scarborough, Scarborough, ON M1C 1A4, Canada.
      Authors
    • Sarajideen S 4
    (1 author)
  • 5. McGill University Health Centre, Montreal, QC H4A 3J1, Canada.
      Authors
    • Simon MM 5
    • Kwan T 5
    (2 authors)
    • Show all (7)

Developmental Cell, 14 Oct 2024, :S1534-5807(24)00574-4
https://doi.org/10.1016/j.devcel.2024.09.024 PMID: 39413784 

Abstract 

The mechanisms that ensure developmental progression in the early human embryo remain largely unknown. Here, we show that the family of long interspersed nuclear element 1 (LINE1) transposons prevents the reversion of naive human embryonic stem cells (hESCs) to 8-cell-like cells (8CLCs). LINE1 RNA contributes to maintenance of H3K27me3 levels, particularly at chromosome 19 (Chr19). Chr19 is enriched for key 8C regulators, H3K27me3, and genes derepressed upon LINE1 knockdown or PRC2 inhibition. Moreover, Chr19 is strongly associated with the nucleolus in hESCs but less in 8CLCs. Direct inhibition of PRC2 activity induces the 8C program and leads to a relocalization of Chr19 away from the nucleolus. LINE1 KD or PRC2 inhibition induces nucleolar stress, and disruption of nucleolar architecture is sufficient to de-repress the 8C program. These results indicate that LINE1 RNA and PRC2 maintain H3K27me3-mediated gene repression and 3D nuclear organization to prevent developmental reversion of hESCs.

Full text links 

Read article at publisher's site: https://doi.org/10.1016/j.devcel.2024.09.024

Citations & impact 

This article has not been cited yet.

Impact metrics

Alternative metrics

Altmetric item for https://www.altmetric.com/details/169335062
Altmetric
Discover the attention surrounding your research
https://www.altmetric.com/details/169335062

Similar Articles 

To arrive at the top five similar articles we use a word-weighted algorithm to compare words from the Title and Abstract of each citation.

Funding 

Funders who supported this work.

CIHR

    Natural Sciences and Engineering Research Council of Canada