Proteomics

Dataset Information

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Identification of ubiquitination sites of purified histone H3


ABSTRACT: Histones modulate gene expression by chromatin compaction, regulating numerous processes such as differentiation. However, the mechanisms underlying histone degradation remain elusive. When compared with their differentiated counterparts, immortal human embryonic stem cells (hESCs) have a unique chromatin architecture and low levels of trimethylated histone H3 at lysine 9 (H3K9me3), a heterochromatin-associated modification. Here we assess a link between the intrinsic epigenetic landscape and ubiquitin-proteasome system of hESCs. We find that hESCs exhibit high expression of UBE2K, a ubiquitin-conjugating enzyme. Loss of UBE2K increases the levels of H3K9 trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation. Concomitantly, loss of UBE2K impairs the ability of hESCs to differentiate into neural progenitors with neurogenic properties. Besides H3K9 trimethylation, we find that UBE2K binds histone H3 to induce its polyubiquitination and degradation by the proteasome. Notably, ubc-20, the worm orthologue of UBE2K, also regulates both histone H3 levels and H3K9 trimethylation in C. elegans germline. Thus, our results indicate that UBE2K crosses evolutionary boundaries to promote histone H3 degradation and reduce H3K9me3 repressive marks in immortal cells.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: David Vilchez  

LAB HEAD: David Vilchez

PROVIDER: PXD018621 | Pride | 2020-06-01

REPOSITORIES: Pride

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Publications

The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells.

Fatima Azra A   Irmak Dilber D   Noormohammadi Alireza A   Rinschen Markus M MM   Das Aniruddha A   Leidecker Orsolya O   Schindler Christina C   Sánchez-Gaya Víctor V   Wagle Prerana P   Pokrzywa Wojciech W   Hoppe Thorsten T   Rada-Iglesias Alvaro A   Vilchez David D  

Communications biology 20200525 1


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  ...[more]

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