PXD018625

PXD018625 is an original dataset announced via ProteomeXchange.

Title	Comparison non-targeting hRNA hESCs versus UBE2K shRNA hESCs
Description	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.
HostingRepository	PRIDE
AnnounceDate	2020-06-01
AnnouncementXML	Submission_2020-06-01_06:40:54.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	David Vilchez
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-17 05:33:54	ID requested
⏵ 1	2020-06-01 06:40:55	announced

Fatima A, Irmak D, Noormohammadi A, Rinschen MM, Das A, Leidecker O, Schindler C, S, á, nchez-Gaya V, Wagle P, Pokrzywa W, Hoppe T, Rada-Iglesias A, Vilchez D, The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. Commun Biol, 3(1):262(2020) [pubmed]

submitter keyword: hESCs, histones, ubiquitin proteasome system

David Vilchez
contact affiliation	CECAD Cluster of Excellence, University of Cologne
contact email	dvilchez@uni-koeln.de
lab head
David Vilchez
contact affiliation	University of Cologne
contact email	dvilchez@uni-koeln.de
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2020/06/PXD018625

PRIDE project URI

• PRIDE
  1. PXD018625
     1. Label: PRIDE project
     2. Name: Comparison non-targeting hRNA hESCs versus UBE2K shRNA hESCs