AI Article Synopsis

  • Histones are important for gene expression regulation and chromatin structure, but how they are degraded is not well understood, especially in human embryonic stem cells (hESCs).
  • In hESCs, the enzyme UBE2K is highly expressed and is essential for controlling histone H3 modification; loss of UBE2K leads to increased repression of genes involved in differentiation due to higher levels of a trimethyltransferase called SETDB1.
  • UBE2K not only promotes the breakdown of histone H3 but also influences the levels of repressive H3K9 trimethylation, showing that this mechanism is conserved across species, as seen in worms too.

Article Abstract

Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. Human embryonic stem cells (hESCs) have a unique chromatin architecture characterized by low levels of trimethylated histone H3 at lysine 9 (H3K9me3), a heterochromatin-associated modification. Here we assess the link between the intrinsic epigenetic landscape and ubiquitin-proteasome system of hESCs. We find that hESCs exhibit high expression of the ubiquitin-conjugating enzyme UBE2K. Loss of UBE2K upregulates the trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation. Besides H3K9 trimethylation, UBE2K binds histone H3 to induce its polyubiquitination and degradation by the proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates histone H3 levels and H3K9 trimethylation in Caenorhabditis elegans germ cells. Thus, our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248108PMC
http://dx.doi.org/10.1038/s42003-020-0984-3DOI Listing

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