MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells Journal Article

Authors: Müller, I.; Moroni, A. S.; Shlyueva, D.; Sahadevan, S.; Schoof, E. M.; Radzisheuskaya, A.; Højfeldt, J. W.; Tatar, T.; Koche, R. P.; Huang, C.; Helin, K.
Article Title: MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells
Abstract: Deciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together, our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3. © 2021, The Author(s).
Keywords: genetics; mutation; cell proliferation; mouse; animal; metabolism; animals; mice; gene expression; protein; protein p53; dna methylation; dna; epigenesis, genetic; histone-lysine n-methyltransferase; phosphoproteins; tumor suppressor protein p53; pluripotent stem cell; pluripotent stem cells; gene knock-in techniques; genetic epigenesis; phosphoprotein; histone lysine methyltransferase; cell; hek293 cells; long interspersed nucleotide elements; mouse embryonic stem cells; humans; human; hek293 cell line; crispr cas system; mouse embryonic stem cell; crispr-cas systems; gene knock-in; mphosph8 protein, mouse; setdb1 protein, human; long interspersed nuclear element
Journal Title: Nature Communications
Volume: 12
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2021-05-24
Start Page: 3034
Language: English
DOI: 10.1038/s41467-021-23308-4
PUBMED: 34031396
PROVIDER: scopus
PMCID: PMC8144423
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Richard Patrick Koche
    149 Koche
  2. Kristian Helin
    31 Helin
  3. Iris Muller
    4 Muller
  4. Chang Huang
    2 Huang