Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Fatima, Azra UNSPECIFIED UNSPECIFIED UNSPECIFIED Irmak, Dilber UNSPECIFIED UNSPECIFIED UNSPECIFIED Noormohammadi, Alireza UNSPECIFIED UNSPECIFIED UNSPECIFIED Rinschen, Markus M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Das, Aniruddha UNSPECIFIED orcid.org/0000-0002-7704-3573 UNSPECIFIED Leidecker, Orsolya UNSPECIFIED UNSPECIFIED UNSPECIFIED Schindler, Christina UNSPECIFIED UNSPECIFIED UNSPECIFIED Sanchez-Gaya, Victor UNSPECIFIED UNSPECIFIED UNSPECIFIED Wagle, Prerana UNSPECIFIED UNSPECIFIED UNSPECIFIED Pokrzywa, Wojciech UNSPECIFIED orcid.org/0000-0002-5110-4462 UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED Rada-Iglesias, Alvaro UNSPECIFIED UNSPECIFIED UNSPECIFIED Vilchez, David UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-REPAIR; PLURIPOTENT; EXPRESSION; LIGASE; GENE; METHYLTRANSFERASE; UBIQUITYLATION; QUANTIFICATION; DEGRADATION; MECHANISMS Multiple languages Biology; Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/33294