TonEBP increases TRIM37
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA896497 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22123183_1.fastq.gz | Fastqsanger.gz | |||
| SRR22123183_2.fastq.gz | Fastqsanger.gz | |||
| SRR22123184_1.fastq.gz | Fastqsanger.gz | |||
| SRR22123184_2.fastq.gz | Fastqsanger.gz | |||
| SRR22123185_1.fastq.gz | Fastqsanger.gz |
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Project description:Aging-related microglial activation is associated with dendritic regression and spine loss in the aged brain. However, the microglia-mediated reductions of spine densities by Tonicity-responsive enhancer-binding protein (TonEBP) in the aged brain is yet unknown. We began to address this question by examining the effect of age on microglial activation and the TonEBP expression in mice. by using molecular and morphologic approaches, the roles of TonEBP in microglial activation and dendritic spines were examined in 12-month-old mice and Alzheimer's diseases (AD) mouse models. Here, we found the increased TonEBP in the hippocampus of aged mice and frontal cortex of AD patients. TonEBP haploinsufficiency reduced microglial activation and dendritic spine regression in 12-month aged mice compared to wild-type (WT) mice. We performed electron microscopy to supply interactions with microglial and synapses. We analyzed microglial processes and extracellular space in areas contacting spines and axon terminal, synaptic cleft, among the hippocampus CA1 of 12-month-old TonEBP haploinsufficient mice versus wild-type littermates. Furthermore, in amyloid-ꞵ oligomer (AꞵO)-injected AD mouse model, TonEBP haploinsufficiency inhibited the dendritic spine loss and improved memory deficits in AβO-treated mice compared to WT mice. These findings indicate that TonEBP may play an important role in aging-induced microglial activation and memory deficits.
2024-12-31 | GSE216976 | GEO
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation. Quadruplicate samples were collected for each condition and then pooled into a single sample for hybridization to microarrays.
2010-12-10 | E-GEOD-25816 | biostudies-arrayexpress
Project description:The TRIM37 gene is mutatedin Mulbery nanism, a rare autosomal recessive disorder, and is in the 17q23 chromosomal region that is amplified in up to ~40% of breast cancers. Trim37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but the protein substrate(s) of Trim37 is unknown. Mono-ubiquitination of histone H2A is a chromatin modification associated with transcriptional repression and here we report that Trim37 is an H2A ubiquitin ligase. Genome-wide Chip-CHIP experiments indicate that in human breast cancer cells containing amplified 17q23, Trim37 is bound to the promoters of many tumor suppressor genes. RNA interference (RNAi)-mediated knockdown of Trim37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2, and transcriptional reactivation of silenced genes. Knockdown of Trim37 in human breast cancer cells containing amplified 17q23 substantially decreases tumor growth in mouse xenografts. Collectively, our results reveal Trim37 as a new H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and redirects PRC2 to silence tumor suppressors and other genes resulting in oncogenesis. Identification of TRIM37 Binding targets in MCF7 cells from the two replicate experiments
2014-10-06 | E-GEOD-48196 | biostudies-arrayexpress
Project description:The TRIM37 gene is mutatedin Mulbery nanism, a rare autosomal recessive disorder, and is in the 17q23 chromosomal region that is amplified in up to ~40% of breast cancers. Trim37 contains a RING finger domain, a hallmark of E3 ubiquitin ligases, but the protein substrate(s) of Trim37 is unknown. Mono-ubiquitination of histone H2A is a chromatin modification associated with transcriptional repression and here we report that Trim37 is an H2A ubiquitin ligase. Genome-wide Chip-CHIP experiments indicate that in human breast cancer cells containing amplified 17q23, Trim37 is bound to the promoters of many tumor suppressor genes. RNA interference (RNAi)-mediated knockdown of Trim37 results in loss of ubiquitinated H2A, dissociation of PRC1 and PRC2, and transcriptional reactivation of silenced genes. Knockdown of Trim37 in human breast cancer cells containing amplified 17q23 substantially decreases tumor growth in mouse xenografts. Collectively, our results reveal Trim37 as a new H2A ubiquitin ligase that is overexpressed in a subset of breast cancers and redirects PRC2 to silence tumor suppressors and other genes resulting in oncogenesis.
2014-10-06 | GSE48196 | GEO
Project description:TonEBP is a transcription factor that promotes cellular accumulation of organic osmolytes in the hypertonic renal medulla by stimulating expression of its target genes. Genetically modified animals with deficient TonEBP activity in the kidney suffer from severe medullary atrophy in association with cell death, demonstrating that TonEBP is essential for the survival of the renal medullary cells. Using both TonEBP knockout cells and RNA interference of TonEBP, we found that TonEBP promoted cellular adaptation to hypertonic stress. Microarray analyses revealed that genetic response to hypertonicity was dominated by TonEBP in that expression of totally different sets of genes was increased by hypertonicity in those cells with TonEBP vs. those without TonEBP activity. Out of over 100 potentially new TonEBP regulated genes, we selected 7 for further analyses and found that their expression was all dependent on TonEBP. RNA interference experiments showed that some of these genes – asporin, insulin-like growth factor-binding protein 5 and 7, and an extracellular lysophosphlipase D – plus Hsp70, a known TonEBP target gene, contributed to the adaptation to hypertonicity without promoting organic osmolyte accumulation. We conclude that TonEBP stimulates multiple cellular pathways for adaptation to hypertonic stress in addition to organic osmolyte accumulation.
2010-12-10 | GSE25816 | GEO
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 37 (TRIM37) as a novel transcriptional coactivator of AP-2γ. We demonstrate TRIM37 facilitates AP-2γ chromatin binding to regulate the AP-2γ mediated transcriptional program directly. We provide evidence that TRIM37 achieves this by stimulating K63-chain-linked polyubiquitination of AP-2γ, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that TRIM37-AP-2γ interaction is essential for breast cancer tumor growth. Overall, our work revealed that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.
2022-07-25 | GSE182546 | GEO
Project description:TRIM37 is a histone H2A ubiquitin ligase importantin breast cancer oncogenesis. To assess the neoplastic transformationsof normal breast epithelial cells in the context of TRIM37, we increased its expression and compared the gene expression network regulated by TRIM37 in control and TRIM37 overexpression.
2025-01-15 | GSE277029 | GEO
Project description:Centrosomes ensure accurate chromosome segregation during cell division. Although the regulation of centrosome number is well-established, less is known about the suppression of non-centrosomal Microtubule-Organising Centres (ncMTOCs). The E3 ligase TRIM37, implicated in Mulibrey nanism and 17q23-amplified cancers, has emerged as a key regulator of both centrosomes and ncMTOCs. Yet, the mechanism by which TRIM37 achieves enzymatic activation to target these mesoscale structures had thus far remained unknown. Here, we elucidate the activation process of TRIM37, unveiling a process that initiates with TRAF domain-directed substrate recognition, followed by B-box domain-mediated oligomerisation, and culminates in RING domain dimerisation. Using optogenetics, we demonstrate that the E3 activity of TRIM37 is directly coupled to the assembly state of its substrates, being activated only when centrosomal proteins cluster into higher-order assemblies resembling MTOCs. This regulatory framework provides a mechanistic basis for understanding TRIM37-driven pathologies and echoes the restriction of the HIV capsid by TRIM5, thus unveiling a conserved activation blueprint among TRIM proteins to control turnover of complexes assembled at the mesoscale level.
2025-03-18 | PXD061083 | Pride
Project description:Using a proteomics approach, we identified the Tripartite Motif Containing 37 (TRIM37) as a novel transcriptional coactivator of AP-2γ. We demonstrate TRIM37 facilitates AP-2γ chromatin binding to regulate the AP-2γ mediated transcriptional program directly. We provide evidence that TRIM37 achieves this by stimulating K63-chain-linked polyubiquitination of AP-2γ, promoting protein localization from the cytoplasm to the nucleus. In clinical analyses, we find TRIM37 is upregulated in multiple breast cancer datasets, supporting our findings that TRIM37-AP-2γ interaction is essential for breast cancer tumor growth. Overall, our work revealed that TRIM37 is an oncogenic coactivator of AP-2γ in breast cancer and provides a novel therapeutic target for treating the disease.
2022-07-25 | GSE182545 | GEO
Project description:TRIM37 is histon H2A ubiquitinase and important oncogene for breast cancer. To test what is the gene expression network regulated by TRIM37, we silenced its ixpression in MDA-MB-231_2b Triple Negative Breast Cancer (TNBC) cell line.
2022-08-31 | GSE136617 | GEO