Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146704 | GEO | 2020/04/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

Project description: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.

| S-EPMC7248108 | biostudies-literature

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [RNA-Seq]

Project description:We find that loss of UBE2K leads to accumulation of histone leading to increase in overall load for epigenetic marks and thus hindering differentiation.Our results provide a novel link between ubiquitination, histone regulation and hESC differentiation into neurons. To test whether UBE2K knockdown also induces enrichment of H3K9me3 marks at specific genes, we performed chromatin immunoprecipitation (ChIP)-sequencing assays of hESCs using an antibody to H3K9me3.

2020-04-22 | GSE146701 | GEO

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [ChIP-Seq]

2020-04-22 | GSE146703 | GEO

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells

Project description:Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells

| PRJNA611702 | ENA

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [RNA-Seq]

Project description:Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [RNA-Seq]

| PRJNA611705 | ENA

Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [ChIP-Seq]

Project description:Regulation of histone H3 by the ubiquitin-conjugating enzyme UBE2K determines neurogenesis of human embryonic stem cells [ChIP-Seq]

| PRJNA611708 | ENA

Regulation of hematopoiesis by the K63-specific ubiquitin-conjugating enzyme Ubc13.

Project description:The ubiquitin-conjugating enzyme Ubc13 mediates lysine-63-specific protein ubiquitination involved in signal transduction by immune receptors; however, the in vivo physiological functions of Ubc13 remain incompletely understood. Using Ubc13 conditional knockout mice, we show that somatic deletion of the Ubc13 gene causes severe loss of multi lineages of immune cells, which is associated with profound atrophy of the thymus and bone marrow, as well as lethality of the mice. Ubc13 has a cell-intrinsic function in mediating hematopoiesis and is essential for the survival and accumulation of hematopoietic stem cells in the bone marrow. Interestingly, loss of Ubc13 results in accumulation of beta-catenin and hyperexpression of Wnt target genes, a condition known to cause impaired hematopoiesis. These results establish Ubc13 as a crucial regulator of hematopoiesis and suggest a role for Ubc13 in the control of Wnt signaling in hematopoietic stem cells.

| S-EPMC2791607 | biostudies-literature

Ubiquitin in motion: structural studies of the ubiquitin-conjugating enzyme?ubiquitin conjugate.

Project description:Ubiquitination of proteins provides a powerful and versatile post-translational signal in the eukaryotic cell. The formation of a thioester bond between ubiquitin (Ub) and the active site of a ubiquitin-conjugating enzyme (E2) is critical for the transfer of Ub to substrates. Assembly of a functional ubiquitin ligase (E3) complex poised for Ub transfer involves recognition and binding of an E2?Ub conjugate. Therefore, full characterization of the structure and dynamics of E2?Ub conjugates is required for further mechanistic understanding of Ub transfer reactions. Here we present characterization of the dynamic behavior of E2?Ub conjugates of two human enzymes, UbcH5c?Ub and Ubc13?Ub, in solution as determined by nuclear magnetic resonance and small-angle X-ray scattering. Within each conjugate, Ub retains great flexibility with respect to the E2, indicative of highly dynamic species that adopt manifold orientations. The population distribution of Ub conformations is dictated by the identity of the E2: the UbcH5c?Ub conjugate populates an array of extended conformations, and the population of Ubc13?Ub conjugates favors a closed conformation in which the hydrophobic surface of Ub faces helix 2 of Ubc13. We propose that the varied conformations adopted by Ub represent available binding modes of the E2?Ub species and thus provide insight into the diverse E2?Ub protein interactome, particularly with regard to interaction with Ub ligases.

| S-EPMC3056393 | biostudies-literature

Cathepsin L proteolytically processes histone H3 during mouse embryonic stem cell differentiation.

Project description:Chromatin undergoes developmentally-regulated structural and chemical changes as cells differentiate, which subsequently lead to differences in cellular function by altering patterns of gene expression. To gain insight into chromatin alterations that occur during mammalian differentiation, we turned to a mouse embryonic stem cell (ESC) model. Here we show that histone H3 is proteolytically cleaved at its N-terminus during ESC differentiation. We map the sites of H3 cleavage and identify Cathepsin L as a protease responsible for proteolytically processing the N-terminal H3 tail. In addition, our data suggest that H3 cleavage may be regulated by covalent modifications present on the histone tail itself. Our studies underscore the intriguing possibility that histone proteolysis, brought about by Cathepsin L and potentially other family members, plays a role in development and differentiation that was not previously recognized.

| S-EPMC2579750 | biostudies-literature

Ubiquitin-specific protease 7 is a regulator of ubiquitin-conjugating enzyme UbE2E1.

Project description:Ubiquitin-specific protease 7 (USP7) is a deubiquitinating enzyme found in all eukaryotes that catalyzes the removal of ubiquitin from specific target proteins. Here, we report that UbE2E1, an E2 ubiquitin conjugation enzyme with a unique N-terminal extension, is a novel USP7-interacting protein. USP7 forms a complex with UbE2E1 in vitro and in vivo through the ASTS USP7 binding motif within its N-terminal extension in an identical manner with other known USP7 binding proteins. We show that USP7 attenuates UbE2E1-mediated ubiquitination, an effect that requires the N-terminal ASTS sequence of UbE2E1 as well as the catalytic activity of USP7. Additionally, USP7 is critical in maintaining the steady state levels of UbE2E1 in cells. This study reveals a new cellular mechanism that couples the opposing activities of the ubiquitination machinery and a deubiquitinating enzyme to maintain and modulate the dynamic balance of the ubiquitin-proteasome system.

| S-EPMC3675629 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data