دورية أكاديمية
Whole-genome doubling drives oncogenic loss of chromatin segregation.
| العنوان: | Whole-genome doubling drives oncogenic loss of chromatin segregation. |
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| المؤلفون: | Lambuta, R.A., Nanni, L., Liu, Y., Diaz-Miyar, J., Iyer, A., Tavernari, D., Katanayeva, N., Ciriello, G., Oricchio, E. |
| المصدر: | Nature, vol. 615, no. 7954, pp. 925-933 |
| سنة النشر: | 2023 |
| المجموعة: | Université de Lausanne (UNIL): Serval - Serveur académique lausannois |
| مصطلحات موضوعية: | Humans, Chromatin/genetics, Chromatin/metabolism, Chromosome Aberrations, Neoplasms/genetics, Chromosomes, Human/genetics, Genome, Chromosome Segregation/genetics, Carcinogenesis/genetics, Epigenesis, Genetic, Disease Progression, Transcription, Gene Expression Regulation, Neoplastic |
| الوصف: | Whole-genome doubling (WGD) is a recurrent event in human cancers and it promotes chromosomal instability and acquisition of aneuploidies 1-8 . However, the three-dimensional organization of chromatin in WGD cells and its contribution to oncogenic phenotypes are currently unknown. Here we show that in p53-deficient cells, WGD induces loss of chromatin segregation (LCS). This event is characterized by reduced segregation between short and long chromosomes, A and B subcompartments and adjacent chromatin domains. LCS is driven by the downregulation of CTCF and H3K9me3 in cells that bypassed activation of the tetraploid checkpoint. Longitudinal analyses revealed that LCS primes genomic regions for subcompartment repositioning in WGD cells. This results in chromatin and epigenetic changes associated with oncogene activation in tumours ensuing from WGD cells. Notably, subcompartment repositioning events were largely independent of chromosomal alterations, which indicates that these were complementary mechanisms contributing to tumour development and progression. Overall, LCS initiates chromatin conformation changes that ultimately result in oncogenic epigenetic and transcriptional modifications, which suggests that chromatin evolution is a hallmark of WGD-driven cancer. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0028-0836 |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/36922594; info:eu-repo/semantics/altIdentifier/eissn/1476-4687; info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_4691B7A968A09; https://serval.unil.ch/notice/serval:BIB_4691B7A968A0Test; urn:issn:0028-0836; https://serval.unil.ch/resource/serval:BIB_4691B7A968A0.P001/REF.pdfTest; http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4691B7A968A09Test |
| DOI: | 10.1038/s41586-023-05794-2 |
| الإتاحة: | https://doi.org/10.1038/s41586-023-05794-2Test https://serval.unil.ch/notice/serval:BIB_4691B7A968A0Test https://serval.unil.ch/resource/serval:BIB_4691B7A968A0.P001/REF.pdfTest http://nbn-resolving.org/urn/resolver.pl?urn=urn:nbn:ch:serval-BIB_4691B7A968A09Test |
| حقوق: | info:eu-repo/semantics/openAccess ; CC BY 4.0 ; https://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.A51721BA |
| قاعدة البيانات: | BASE |
| تدمد: | 00280836 |
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| DOI: | 10.1038/s41586-023-05794-2 |