Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNF20 and USP44 regulate embryonic stem cell differentiation by modulating H2B monoubiquitylation

ABSTRACT: Embryonic stem cells (ESCs) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2BK120ub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of long genes during ESC differentiation. Furthermore, we identify USP44 as a deubiquitinase whose downregulation by differentiation signals contributes to the increase in H2BK120ub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.

ORGANISM(S): Homo sapiens

PROVIDER: GSE33214 | GEO | 2013/01/03

SECONDARY ACCESSION(S): PRJNA149441

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RNF20 and USP44 regulate embryonic stem cell differentiation by modulating H2B monoubiquitylation

Project description:Embryonic stem cells (ESCs) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2BK120ub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of long genes during ESC differentiation. Furthermore, we identify USP44 as a deubiquitinase whose downregulation by differentiation signals contributes to the increase in H2BK120ub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. RNF20 depleted or control NTera2 cells stimulated with RA for 72 hours

2013-01-03 | E-GEOD-33214 | biostudies-arrayexpress

RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation.

Project description:Embryonic stem cells (ESCs) maintain high genomic plasticity, which is essential for their capacity to enter diverse differentiation pathways. Posttranscriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner.

| S-EPMC3374598 | biostudies-literature

USP44 overexpression drives a MYC-like gene expression program in neuroblastoma through epigenetic reprogramming

Project description:Neuroblastoma is an embryonic cancer that disproportionately contributes to death in young children. Sequencing data have uncovered few recurrently mutated genes in this cancer though epigenetic pathways have been implicated in disease pathogenesis. We performed a computational screen of deubiquitinating enzymes to identify potential new targets and identified the histone H2B deubiquitinating enzyme USP44 as significantly over-expressed in high-risk tumors. High levels of USP44 significantly correlate with metastatic disease, unfavorable histology, advanced patient age, and MYCN-amplification. The subset of patients with tumors expressing high levels of USP44 have a significantly worse survival, including those with tumors lacking MYCN-amplification. Depleting USP44 in neuroblastoma cell lines leads to diminished proliferation, migration, invasion, as well as impaired neuritic development in response to retinoic acid. Integrated analysis of RNA-seq and ChIP-seq demonstrates a distinct set of genes that is regulated by USP44, including those in Hallmark pathways critical to tumorigenesis – findings that were completely reversed by the re-introduction of USP44. We conclude that USP44 is a novel epigenetic regulator that restrains differentiation and promotes aggressive features. Our data further suggests that USP44 may be a novel target in this disease.

2024-06-11 | GSE228130 | GEO

USP44 overexpression drives a MYC-like gene expression program in neuroblastoma through epigenetic reprogramming

2024-06-11 | GSE228131 | GEO

USP44 overexpression drives a MYC-like gene expression program in neuroblastoma through epigenetic reprogramming

2024-06-11 | GSE262506 | GEO

Homo sapiens

Project description:RNF20 and USP44 regulate embryonic stem cell differentiation by modulating H2B monoubiquitylation

| PRJNA149441 | ENA

Co-transcriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate

Project description:Various histone modifications decorate nucleosomes within transcribed genes. Among these, monoubiquitylation of histone H2B (H2Bub1) and methylation of histone H3 on lysines 36 (H3K36me2/3) and 79 (H3K79me2/3) correlate positively with gene expression. By measuring the progression of the transcriptional machinery along genes within live cells, we now report that H2B monoubiquitylation occurs co-transcriptionally and accurately reflects the advance of RNA polymerase II (Pol II). In contrast, H3K36me3 and H3K79me2 are less dynamic and represent Pol II movement less faithfully. High resolution ChIP-seq reveals that H2Bub1 levels are selectively reduced at exons, and decrease in an exon-dependent stepwise manner towards the 3' end of genes. Exonic depletion of H2Bub1 in gene bodies is highly correlated with Pol II pausing at exons, suggesting elongation rate changes associated with intron-exon structure. Overall, our data shed light on the organization of H2Bub1 within transcribed genes, and single out H2Bub1 as a reliable marker for ongoing transcription elongation. H2Bub1 and H2B ChIP-seq in NT2 cells

2014-07-15 | E-GEOD-56279 | biostudies-arrayexpress

Co-transcriptional histone H2B monoubiquitylation is tightly coupled with RNA polymerase II elongation rate

2014-07-15 | GSE56279 | GEO

Usp44 binds centrin to regulate centrosome positioning and suppress tumorigenesis

Project description:Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy through restraining the activity of the anaphase-promoting complex (APC). USP44 was identified as a key regulator of APC activation that maintains the association of MAD2 with the APC co-activator Cdc20. However, the physiological importance of USP44 and its impact on cancer biology are unknown. Here, we show that USP44 is required to prevent tumors in mice and is frequently down-regulated in human lung cancer. USP44 inhibits chromosome segregation errors independently of its role in the mitotic checkpoint by regulating proper centrosome separation, positioning, and mitotic spindle geometry, functions that require direct binding to the centriole protein, centrin. These data reveal a new role for the ubiquitin system in mitotic spindle regulation and underscore the importance of USP44 in the pathogenesis of human cancer. Study included 100 non-neoplastic (N) lung samples, and 69, 12, and 13 stage I, II, and II lung adenocarcinoma (AD) frozen tissues, respectively. Expression levels of Usp44 in different stages of AD was compared against N.

2013-09-01 | E-GEOD-40791 | biostudies-arrayexpress

Usp44 binds centrin to regulate centrosome positioning and suppress tumorigenesis

2013-09-01 | GSE40791 | GEO