Fatima, Azra, Irmak, Dilber, Noormohammadi, Alireza, Rinschen, Markus M., Das, Aniruddha ORCID: 0000-0002-7704-3573, Leidecker, Orsolya, Schindler, Christina, Sanchez-Gaya, Victor, Wagle, Prerana, Pokrzywa, Wojciech ORCID: 0000-0002-5110-4462, Hoppe, Thorsten ORCID: 0000-0002-4734-9352, Rada-Iglesias, Alvaro and Vilchez, David (2020). The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. Commun. Biol., 3 (1). NEW YORK: NATURE PUBLISHING GROUP. ISSN 2399-3642

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Abstract

Azra Fatima et al. show that ubiquitin-conjugating enzyme UBE2K regulates neurogenic potential through its target histone H3 in human embryonic stem cells. This study suggests that UBE2K promotes histone H3 degradation, reducing the H3K9me3 repressive marks in immortal cells of both worms and humans. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Fatima, AzraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Irmak, DilberUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noormohammadi, AlirezaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rinschen, Markus M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Das, AniruddhaUNSPECIFIEDorcid.org/0000-0002-7704-3573UNSPECIFIED
Leidecker, OrsolyaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schindler, ChristinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sanchez-Gaya, VictorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wagle, PreranaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pokrzywa, WojciechUNSPECIFIEDorcid.org/0000-0002-5110-4462UNSPECIFIED
Hoppe, ThorstenUNSPECIFIEDorcid.org/0000-0002-4734-9352UNSPECIFIED
Rada-Iglesias, AlvaroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Vilchez, DavidUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-332949
DOI: 10.1038/s42003-020-0984-3
Journal or Publication Title: Commun. Biol.
Volume: 3
Number: 1
Date: 2020
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 2399-3642
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
DNA-REPAIR; PLURIPOTENT; EXPRESSION; LIGASE; GENE; METHYLTRANSFERASE; UBIQUITYLATION; QUANTIFICATION; DEGRADATION; MECHANISMSMultiple languages
Biology; Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/33294

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