Oncogenic lncRNAs alter epigenetic memory at a fragile chromosomal site in human cancer cells. 2022

Ganesan Arunkumar, and Songjoon Baek, and David Sturgill, and Minh Bui, and Yamini Dalal
Laboratory of Receptor Biology and Gene Expression, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892, USA.

Chromosome instability is a critical event in cancer progression. Histone H3 variant CENP-A plays a fundamental role in defining centromere identity, structure, and function but is innately overexpressed in several types of solid cancers. In the cancer background, excess CENP-A is deposited ectopically on chromosome arms, including 8q24/cMYC locus, by invading transcription-coupled H3.3 chaperone pathways. Up-regulation of lncRNAs in many cancers correlates with poor prognosis and recurrence in patients. We report that transcription of 8q24-derived oncogenic lncRNAs plays an unanticipated role in altering the 8q24 chromatin landscape by H3.3 chaperone-mediated deposition of CENP-A-associated complexes. Furthermore, a transgene cassette carrying specific 8q24-derived lncRNA integrated into a naïve chromosome locus recruits CENP-A to the new location in a cis-acting manner. These data provide a plausible mechanistic link between locus-specific oncogenic lncRNAs, aberrant local chromatin structure, and the generation of new epigenetic memory at a fragile site in human cancer cells.

UI MeSH Term Description Entries
D009369 Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Neoplasm,Cancer,Malignant Neoplasm,Tumor,Tumors,Benign Neoplasms,Malignancy,Malignant Neoplasms,Neoplasia,Neoplasm,Neoplasms, Benign,Cancers,Malignancies,Neoplasias,Neoplasm, Benign,Neoplasm, Malignant,Neoplasms, Malignant
D002503 Centromere The clear constricted portion of the chromosome at which the chromatids are joined and by which the chromosome is attached to the spindle during cell division. Centromeres
D002843 Chromatin The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell. Chromatins
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000076247 Centromere Protein A A 17 kDa, centromeric, poly(ADP)-ribose binding protein that is structurally similar to HISTONE H3 and localizes to NUCLEOSOMES within the CENTROMERE; specifically within the region that binds KINETOCHORES, where it replaces histone H3. It plays a critical role in recruiting kinetochore proteins and progression through MITOSIS, chromosome segregation, and CYTOKINESIS. It also binds sera from patients with some scleroderma-like AUTOIMMUNE DISEASES. CENP-A Protein,CENPA Protein,Centromere Autoantigens 17K,Centromere Protein 17K,Autoantigens 17K, Centromere,CENP A Protein
D044127 Epigenesis, Genetic A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression. Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics
D062085 RNA, Long Noncoding A class of untranslated RNA molecules that are typically greater than 200 nucleotides in length and do not code for proteins. Members of this class have been found to play roles in transcriptional regulation, post-transcriptional processing, CHROMATIN REMODELING, and in the epigenetic control of chromatin. LincRNA,RNA, Long Untranslated,LINC RNA,LincRNAs,Long Intergenic Non-Protein Coding RNA,Long Non-Coding RNA,Long Non-Protein-Coding RNA,Long Noncoding RNA,Long ncRNA,Long ncRNAs,RNA, Long Non-Translated,lncRNA,Long Intergenic Non Protein Coding RNA,Long Non Coding RNA,Long Non Protein Coding RNA,Long Non-Translated RNA,Long Untranslated RNA,Non-Coding RNA, Long,Non-Protein-Coding RNA, Long,Non-Translated RNA, Long,Noncoding RNA, Long,RNA, Long Non Translated,RNA, Long Non-Coding,RNA, Long Non-Protein-Coding,Untranslated RNA, Long,ncRNA, Long,ncRNAs, Long
D063646 Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Tumorigenesis,Oncogenesis,Carcinogeneses,Oncogeneses,Tumorigeneses

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