Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA312307 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:A commonly inactivated tumor suppressor silences endogenous retroelements in somatic cells [ChIP-Seq]
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Project description:A commonly inactivated tumor suppressor silences endogenous retroelements in somatic cells
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Project description:A commonly inactivated tumor suppressor silences endogenous retroelements in somatic cells [Affymetrix expression]
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Project description:STK11 (LKB1) missense somatic mutant isoforms promote tumor growth, motility and inflammation. Elucidating the contribution of somatic mutations to cancer is essential for personalized medicine. STK11 (LKB1) tumor suppressor appears to be inactivated in human cancer, however, somatic missense mutations also occur. Despite of our increased knowledge about LKB1 function, the role/s of these alterations in cancer are mostly unknown. Here, we investigated the contribution of four missense LKB1 somatic mutations in tumor biology. Three, out of the four mutants, lost their tumor suppressor capabilities and showed a deficient kinase activity. The remaining mutant conserved the enzymatic activity, but conferred an increased cell motility. Mechanistically, LKB1 mutants promoted the differential gene expression regulation of vesicle trafficking regulating molecules, adhesion molecules and cytokines, that correlated with the identified protein networks associated to the comparative secretome analysis. Notably, three mutant isoforms promoted tumor growth, and one of them induced inflammation and hemorrhagic tumors that correlated with the deregulated levels of cytokines. Altogether, our findings uncover oncogenic roles of LKB1 somatic mutations helping to understand their contribution to cancer.
2021-09-09 | PXD018041 | Pride
Project description:p53 is a potent tumor suppressor and commonly mutated in human cancers. Recently, we demonstrated that p53 genes act to restrict retrotransposons in germ line tissues of flies and fish but whether this activity is conserved in somatic human cells is not known. Here we show that p53 constitutively restrains human LINE1s by cooperatively engaging sites in the 5’UTR and stimulating local deposition of repressive histone marks at these transposons. Consistent with this, the elimination of p53 or the removal of corresponding binding sites in LINE1s, prompted these retroelements to become hyperactive. Concurrently, p53 loss instigated chromosomal rearrangements linked to LINE sequences and also provoked inflammatory programs that were dependent on reverse transcriptase produced from LINE1s. Taken together, our observations establish that p53 continuously operates at the LINE1 promoter to restrict autonomous copies of these mobile elements in human cells. Our results further suggest that constitutive restriction of these retroelements may help to explain tumor suppression encoded by p53, since erupting LINE1s produced acute oncogenic threats when p53 was absent.
2020-12-01 | GSE159134 | GEO
Project description:Reverse transcription-derived sequences account for at least half of the human genome. Although these retroelements are formidable motors of evolution, they can occasionally cause disease, and accordingly are inactivated during early embryogenesis through epigenetic mechanisms. In the mouse, at least for endogenous retroviruses, important mediators of this process are the tetrapod-specific KRAB-containing zinc finger proteins (KRAB-ZFPs) and their cofactor TRIM28. The present study demonstrates that KRAB/TRIM28-mediated regulation is responsible for controlling a very broad range of human-specific endogenous retroelements (EREs) in human embryonic stem (ES) cells and that it exerts, as a consequence, a marked effect on the transcriptional dynamics of these cells. It further reveals reciprocal dependence between TRIM28 recruitment at specific families of EREs and DNA methylation. It finally points to the importance of persistent TRIM28-mediated control of ERE transcriptional impact beyond their presumed inactivation by DNA methylation. Analyses of epigentic effectors and marks in KAP1 WT and KD human embryonic stem cells
2014-05-29 | E-GEOD-57989 | biostudies-arrayexpress
Project description:Morc3 silences endogenous retroviruses in mouse embryonic stem cells [H3K9me3 ChIP-seq]
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Project description:Morc3 silences endogenous retroviruses by enabling Daxx-mediated H3.3 incorporation [ChIP-seq]
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Project description:Morc3 silences endogenous retroviruses in mouse embryonic stem cells [Morc3 ChIP-seq]
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Project description:USP7, which encodes a deubiquitylating enzyme, is among the most frequently mutated genes in pediatric T-ALL, with somatic heterozygous loss-of-function mutations (haploinsufficiency) predominantly affecting the subgroup that has aberrant TAL1 oncogene activation. Network analysis of >200 T-ALL transcriptomes linked USP7 haploinsufficiency with decreased activities of E-proteins. E-proteins are also negatively regulated by TAL1, leading to concerted down-regulation of E-protein target genes involved in T-cell development. In T-ALL cell lines, we show the physical interaction of USP7 with E-proteins and TAL1 by mass spectrometry and ChIP-seq. Haploinsufficient but not complete CRISPR knock-out of USP7 shown accelerated cell growth and validated transcriptional down-regulation of E-protein targets. Our study unveiled the synergistic effect of USP7 haploinsufficiency with aberrant TAL1 activation on T-ALL, implicating USP7 as a haploinsufficient tumor suppressor in T-ALL.
2021-03-16 | PXD023377 | Pride