The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells
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The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. / Fatima, Azra; Irmak, Dilber; Noormohammadi, Alireza; Rinschen, Markus M; Das, Aniruddha; Leidecker, Orsolya; Schindler, Christina; Sánchez-Gaya, Víctor; Wagle, Prerana; Pokrzywa, Wojciech; Hoppe, Thorsten; Rada-Iglesias, Alvaro; Vilchez, David.
In: COMMUN BIOL, Vol. 3, No. 1, 25.05.2020, p. 262.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells
AU - Fatima, Azra
AU - Irmak, Dilber
AU - Noormohammadi, Alireza
AU - Rinschen, Markus M
AU - Das, Aniruddha
AU - Leidecker, Orsolya
AU - Schindler, Christina
AU - Sánchez-Gaya, Víctor
AU - Wagle, Prerana
AU - Pokrzywa, Wojciech
AU - Hoppe, Thorsten
AU - Rada-Iglesias, Alvaro
AU - Vilchez, David
PY - 2020/5/25
Y1 - 2020/5/25
N2 - 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.
AB - 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.
U2 - 10.1038/s42003-020-0984-3
DO - 10.1038/s42003-020-0984-3
M3 - SCORING: Journal article
C2 - 32451438
VL - 3
SP - 262
JO - COMMUN BIOL
JF - COMMUN BIOL
SN - 2399-3642
IS - 1
ER -