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Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

ABSTRACT: Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

PROVIDER: PRJNA673703 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12960911_1.fastq.gz	Fastqsanger.gz
	SRR12960911_2.fastq.gz	Fastqsanger.gz
	SRR12960912_1.fastq.gz	Fastqsanger.gz
	SRR12960912_2.fastq.gz	Fastqsanger.gz
	SRR12960913_1.fastq.gz	Fastqsanger.gz

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Similar Datasets

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

Project description:Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

| PRJNA673701 | ENA

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [ATAC-Seq]

Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Yet, information on physiological roles and underlying signaling mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with a novel multiple congenital anomaly disorder caused by hemizygous variants in OTUD5, encoding a K48-/K63-linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of a select group of chromatin regulators. These include ARID1A/B, HDAC2, and HCF1, mutation of which underlie different developmental disorders that exhibit phenotypic overlap with OTUD5 patients. Consequently, loss of OTUD5 during early differentiation leads to less accessible chromatin at neuroectodermal enhancers and thus aberrant rewiring of gene expression networks. Our study describes a novel developmental disorder we name LINKED (LINKage-specific-deubiquitylation-deficiency-induced Embryonic Defects) syndrome, provides a previously unrecognized mechanistic link between phenotypically related diseases, and reveals linkage-specific ubiquitin cleavage from substrate groups (i.e. chromatin remodelers) as an essential mode of signaling required to coordinate embryonic differentiation pathways.

2020-11-02 | GSE160588 | GEO

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

2020-11-02 | GSE160589 | GEO

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

Project description:Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation [RNA-Seq]

| PRJNA673704 | ENA

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation.

Project description:Reversible modification of proteins with linkage-specific ubiquitin chains is critical for intracellular signaling. Information on physiological roles and underlying mechanisms of particular ubiquitin linkages during human development are limited. Here, relying on genomic constraint scores, we identify 10 patients with multiple congenital anomalies caused by hemizygous variants in OTUD5, encoding a K48/K63 linkage-specific deubiquitylase. By studying these mutations, we find that OTUD5 controls neuroectodermal differentiation through cleaving K48-linked ubiquitin chains to counteract degradation of select chromatin regulators (e.g., ARID1A/B, histone deacetylase 2, and HCF1), mutations of which underlie diseases that exhibit phenotypic overlap with OTUD5 patients. Loss of OTUD5 during differentiation leads to less accessible chromatin at neuroectodermal enhancers and aberrant gene expression. Our study describes a previously unidentified disorder we name LINKED (LINKage-specific deubiquitylation deficiency-induced Embryonic Defects) syndrome and reveals linkage-specific ubiquitin cleavage from chromatin remodelers as an essential signaling mode that coordinates chromatin remodeling during embryogenesis.

| S-EPMC7817106 | biostudies-literature

Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-11-02 | GSE160590 | GEO

Whole-transcriptome analysis using RNA sequencing in OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells

Project description:Whole-transcriptome analysis was performed on RNA from OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells to identify the cellular processes regulated by OTUD5 and mTOR simultaneously.

2021-03-18 | GSE135078 | GEO

OTUD5 complex mass spectrometry

Project description:DUBs are involved in various pathways and signalling networks by pairing with E3 ubiquitin ligases in protein complexes. In order to test whether OTUD5 associates with an E3 ubiquitin ligase to regulate cell proliferation, the stable Flag-OTUD5/Hep3B cell line was established by transfecting Hep3B cells with plasmids expressing pCIN4-Flag-OTUD5. The cellular factors interacting with OTUD5 were purified by anti-Flag antibody-conjugated M2 beads.

2020-09-11 | PXD019907 | Pride

Autophagy of OTUD5 Destabilizes GPX4 to Confer Ferroptosis-Dependent Kidney Injury

Project description:Ferroptosis is an iron-dependent programmed cell death associated with severe kidney diseases, linked to decreased glutathione peroxidase 4 (GPX4). However, the spatial distribution of renal GPX4-mediated ferroptosis and the molecular events causing GPX4 reduction during ischemia-reperfusion (I/R) remain largely unknown. Using spatial transcriptomics, we identify that GPX4 is situated at the interface of the inner cortex and outer medulla, a hyperactive ferroptosis site post-I/R injury. We show that OTU deubiquitinase 5 (OTUD5) is a GPX4-binding protein that confers ferroptosis resistance by stabilizing GPX4. During I/R, ferroptosis is induced by mTORC1-mediated autophagy, causing OTUD5 degradation and subsequent GPX4 decay. Functionally, OTUD5 deletion intensifies renal tubular cell ferroptosis and exacerbates acute kidney injury, while AAV-mediated OTUD5 delivery mitigates ferroptosis and promotes renal function recovery from I/R injury. In this work, our study highlights a new autophagy-dependent ferroptosis module: hypoxia/ischemia-induced OTUD5 autophagy triggers GPX4 degradation, offering a potential therapeutic avenue for I/R-related kidney diseases.

2023-11-29 | GSE244330 | GEO

Whole-transcriptome analysis using RNA sequencing in OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells

Project description:Whole-transcriptome analysis using RNA sequencing in OTUD5-wild type, OTUD5-null, and GDC0349-treated HEK293 cells

| PRJNA557353 | ENA