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HESCs quantitative proteomic MASS

ABSTRACT: To understand the potential signaling by which the loss of UBQLN1 leads to telomere damage,we performed quantitative proteomic MASS

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: shuang Zhao

LAB HEAD: Zhao shuang

PROVIDER: PXD036642 | Pride | 2024-07-03

REPOSITORIES: pride

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			Action	DRS
	F9526TQB1_1.raw	Raw
	F9526TQB1_10.raw	Raw
	F9526TQB1_11.raw	Raw
	F9526TQB1_12.raw	Raw
	F9526TQB1_13.raw	Raw

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Publications

UBQLN1 links proteostasis and mitochondria function to telomere maintenance in human embryonic stem cells.

Zhao Shuang S Li Jie J Duan Songqi S Liu Chang C Wang Hua H Lu Jiangtao J Zhao Nannan N Sheng Xiaoyan X Wu Yiwei Y Li Yanjun Y Sun Baofa B Liu Lin L

Stem cell research & therapy 20240621 1

<h4>Background</h4>Telomeres consist of repetitive DNA sequences at the chromosome ends to protect chromosomal stability, and primarily maintained by telomerase or occasionally by alternative telomere lengthening of telomeres (ALT) through recombination-based mechanisms. Additional mechanisms that may regulate telomere maintenance remain to be explored. Simultaneous measurement of telomere length and transcriptome in the same human embryonic stem cell (hESC) revealed that mRNA expression levels ...[more]

PMID: 38902824

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Telomere length effect on genes near the telomere in myoblasts

Project description:We examined differential expression of genes within 10MBs of telomeres in myoblasts with long or short telomeres We offer telomere looping with telomere length as a partial mechanistic explanation for the changes gene expression that is observed. Compare expression of genes within 10MB of the telomere in normal myoblasts with long (15 kb) and short (6 kb) telomeres.

2014-07-17 | E-GEOD-48973 | biostudies-arrayexpress

U2OS SLX4IP Knockout Telomere PICh

Project description:This experiment sought to characterize the perturbations to the telomere proteome brought about by modulation of SLX4IP expression, as we have previously found SLX4IP to act as a key regulator of telomere maintenance.

2022-02-16 | PXD024141 | Pride

Npl3 stabilizes R-loops at telomeres to prevent accelerated replicative senescence

Project description:Telomere shortening rates must be regulated to prevent premature replicative senescence. TERRA R-loops become stabilized at critically short telomeres to promote their elongation through homology-directed repair (HDR), thereby counteracting senescence onset. Using a non-bias proteomic approach to identify telomere binding factors, we identified Npl3, an RNA-binding protein previously implicated in multiple RNA biogenesis processes. Using Chromatin- and RNA immunoprecipitation, we demonstrate that Npl3 interacts with TERRA and telomeres. Furthermore, we show that Npl3 associates to telomeres in an R-loop dependent manner, as changes in R-loop levels, e.g. at short telomeres, modulate the recruitment of Npl3 to chromosome ends. Through a series of genetic and biochemical approaches we demonstrate that Npl3 binds to TERRA and stabilizes R-loops at short telomeres, which in turn promotes HDR and prevents premature replicative senescence onset. This may have implications for diseases associated with excessive telomere shortening.

2020-01-31 | PXD016772 | Pride

TEBP-1 and TEBP-2 are double-stranded telomere binders required for fertility

Project description:Telomeres are the ends of linear chromosomes and consist of repetitive double- and single-stranded DNA sequences. Telomeres are bound by dedicated protein complexes, such as shelterin in mammals. In the nematode Caenorhabditis elegans, a comprehensive understanding of the proteins interacting with the telomere sequence is lacking. Here, we harnessed a quantitative proteomics approach to screen for proteins binding to C. elegans telomeres, and identified TEBP-1 and TEBP-2, two paralogs that associate to telomeres in vitro and in vivo. TEBP-1 and TEBP-2 form a telomeric complex with the known single-stranded telomere-binding proteins POT-1, POT-2, and MRT-1. tebp-1 and tebp-2 mutants display strikingly distinct phenotypes: tebp-1 mutants have longer telomeres than wild-type animals, while tebp 2 mutants display shorter telomeres and a mortal germline, a phenotype characterized by transgenerational germline deterioration. Notably, tebp 1;tebp-2 double mutant animals are synthetic sterile, with germlines showing signs of severe mitotic and meiotic arrest. These results define the first telomere-binding complex of C. elegans, including TEBP-1 and TEBP-2, two double-stranded telomere binders required for fertility.

2021-03-09 | PXD019241 | Pride

Zbtb48 is a regulator of Mtfp1 expression in zebrafish

Project description:ZBTB48 (also known as TZAP) is a transcription factor that has previously been reported to bind to telomeres and act as a negative regulator of telomere length in human cell lines. To explore whether transcription factor activity and telomere length regulation are conserved at the organismal level in vertebrates, we generated a zbtb48-/- zebrafish line via CRISPR‒Cas genome editing. The zbtb48-/- mutants displayed no obvious physical or behavioral abnormalities in the first two generations. We found no statistically significant changes in telomere length in first-generation adults. However, for the gene regulatory aspect of Zbtb48, similar to that in human cancer cell lines, we observed downregulation of mtfp1 at both the mRNA and protein levels in the zbtb48-/- mutants. This suggests that mtfp1 is an evolutionarily conserved regulatory target of Zbtb48. Further investigation of the spatiotemporal expression of zbtb48 in previously published zebrafish data revealed low transcript expression in diverse tissues, except in germline stem cells and gametocytes of the gonads. Notably, Mtfp1 protein downregulation was detected in the ovaries of 40 dpf zbtb48-/- mutants and in the testes of both 40 dpf and 10.5-month-old zbtb48-/- mutants.

2025-01-09 | PXD052763 | Pride

Regulation of gene expression through genome-wide co-binding of Hoxa9 and C/EBPα in transformed HSCs

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-06-11 | E-GEOD-58362 | biostudies-arrayexpress

Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice

Project description:Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and to elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of kinases, acetylases, and biomarkers, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity. Six samples were analyzed, in which a control sample was included.

2015-02-18 | E-GEOD-65993 | biostudies-arrayexpress

Gene expression changes after loss of C/EBPα in transformed HSCs [CEBPA RNA-seq]

Project description:RNAseq characterization of gene expression changes 72 hours after genomic excision of Cebpa in murine hematopoietic progenitors from Cebpaf/f;CreER mice transformed by Hoxa9/Meis1. In the presence of tamoxifen (4OHT), Cre-ER localizes to the nucleus of cells allowing for excision of Cebpa and loss of C/EBPα protein levels. Loss of C/EBPα leads to a decrease in cellular proliferation. Examination of gene expression by RNAseq in two conditions in biological replicates.

2014-06-11 | E-GEOD-58360 | biostudies-arrayexpress

Gene expression changes after loss of Hoxa9 in transformed HSCs [HOXA9 RNA-seq]

Project description:Characterization of gene expression changes 72 hours after withdrawal of tamoxifen in murine hematopoietic progenitors transformed by Hoxa9-ER/Meis1 using RNAseq. In the presence of tamoxifen (4OHT), Hoxa9-ER localizes to the nucleus of cells allowing for transformation, while withdrawal of 4OHT (culture in EtOH) leads to loss of nuclear Hoxa9-ER. Loss of Hoxa9-ER leads to a decrease in cellular proliferation and differentiation along the myeloid lineage. Examination of gene expression by RNAseq in two conditions in biological replicates.

2014-06-11 | E-GEOD-58359 | biostudies-arrayexpress

Transcription profiling of mouse heart from MuRF1 MrRF2 doble knockout vs. wildtype to analyze signalling athways involving MurF1 and MuRF2

Project description:Two genes coding for potential muscle signaling proteins were knocked out (MuRF1+2: DKO). RNA of hearts of Wildtype and DKO mice are compared to analyze the signaling pathwayws MuRF1 and MuRF2 are involved in.

2008-03-01 | E-MEXP-1027 | biostudies-arrayexpress

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