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Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

ABSTRACT: Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. We combined Circle-Seq and RNA-Seq to identified crucial extrachromosomal circular oncogene amplicons. Herein, we revealed that extrachromosomal circular SUZ12 amplicon regulates H3K27me3 modification during the oncogenic progression of retinoblastoma. Conclusively, our study initially delineated an integrated picture of the eccDNA landscape in retinoblastoma and unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

ORGANISM(S): Homo sapiens

PROVIDER: GSE235888 | GEO | 2023/07/02

REPOSITORIES: GEO

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Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [CUT&Tag]

Project description:Extrachromosomal circular DNA (eccDNA) is double-stranded circular DNA that is derived from but independent of chromosomal DNA. Owing to its nonchromosomal inheritance, eccDNA facilitates the amplification of oncogenes and expedites the process of genome evolution in tumor. However, the role of eccDNA in RB remains enigmatic. Herein, we identified a set of SUZ12-containing eccDNAs in RB. Through multiomics analyses, we demonstrated that SUZ12 contributes to elevated levels of H3K27me3 modification and subsequently inhibits the transcription of KLF4 during the oncogenic progression of retinoblastoma. Conclusively, our study unveiled a novel SUZ12-containing eccDNA/H3K27me3 oncogenic mechanism where eccDNA dictates retinoblastoma progression through regulating transcription levels of linear DNA.

2023-08-05 | GSE239785 | GEO

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [RNA-seq]

2023-07-02 | GSE235887 | GEO

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

Project description:Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [eccDNA-seq]

| PRJNA987988 | ENA

Transcription-induced formation of extrachromosomal DNA during yeast ageing

Project description:Extrachromosomal circular DNA (eccDNA) facilitates adaptive evolution by allowing rapid and extensive gene copy number variation, and is implicated in the pathology of cancer and ageing. Here, we demonstrate that yeast aged under environmental copper accumulate high levels of eccDNA containing the copper resistance gene CUP1. Transcription of CUP1 causes CUP1 eccDNA accumulation, which occurs in the absence of phenotypic selection. We have developed a sensitive and quantitative eccDNA sequencing pipeline that reveals CUP1 eccDNA accumulation on copper exposure to be exquisitely site specific, with no other detectable changes across the eccDNA complement. eccDNA forms de novo from the CUP1 locus through processing of DNA double-strand breaks (DSBs) by Sae2 / Mre11 and Mus81, and genome-wide analyses show that other protein coding eccDNA species in aged yeast share a similar biogenesis pathway. Although abundant we find that CUP1 eccDNA does not replicate efficiently, and high copy numbers in aged cells arise through frequent formation events combined with asymmetric DNA segregation. The transcriptional stimulation of CUP1 eccDNA formation shows that age-linked genetic change varies with transcription pattern, resulting in gene copy number profiles tailored by environment.

2019-10-18 | GSE135542 | GEO

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation

Project description:Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation

| PRJNA987978 | ENA

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [CUT&Tag]

Project description:Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [CUT&Tag]

| PRJNA1000961 | ENA

Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [RNA-seq]

Project description:Extrachromosomal circular SUZ12 amplicon dictates retinoblastoma progression through reprogramming H3K27 methylation [RNA-seq]

| PRJNA987987 | ENA

Promoterless extrachromosomal circular DNA, microDNA, autonomously produce short regulatory RNAs that suppress gene expression

Project description:Interest in extrachromosomal circular DNA (eccDNA) molecules has increased recently because of their widespread presence in normal cells across every species ranging from yeast to humans, their increased levels in cancer cells, and their overlap with oncogenic and drug-resistant genes. However, the majority of eccDNA are too small to carry protein coding genes and their function has remained unknown. We have tested functional capabilities of small eccDNA molecules, termed microDNA, by creating artificial microDNA molecules mimicking known microDNA sequences and have discovered that microDNA express functional small regulatory RNA including microRNA and novel si-like RNA. MicroDNA is transcribed in vitro and in vivo independent of a promoter sequence. MicroDNA which carry miRNA genes form transcripts which are processed into mature miRNA molecules, through the endogenous RNA-interference pathway, which repress a luciferase reporter gene as well as endogenous mRNA targets of the miRNA. Further, microDNA containing sequences of exons repress the endogenous gene from which the microDNA was derived through the formation of novel si-like RNA. We also show that endogenous microDNA associate with RNA polymerases subunits POLR2H and POLR3F. Together, these results suggest that microDNA actively modulate gene expression through the production of both known and novel regulatory small RNA.

2019-01-28 | GSE124470 | GEO

Identification and characterization of extrachromosomal circular DNA in patients with high myopia and cataract

Project description:To explore the presence of extrachromosomal circular DNA (eccDNA) in the anterior capsule of the lens in the eyes of patients with cataract and with high myopia. Circle-Seq was performed to identify differences in the eccDNA and gene expression between the anterior capsule of the lens of patients with simple nuclear cataract (C, n = 6) and patients with nuclear cataract along with high myopia (HM, n = 6). The expression of eccDNA was confirmed using routine quantitative polymerase chain reaction. The eccDNA ranked in C and HM ranged in length from 0.017 kb – 9.9 Mb with two distinctive peaks detected at 0.2 kb and 0.5 kb, while eccDNA that were differentially expressed (up- and down-regulated) ranged in size from 0.05 kb – 57.8 kb with two distinctive peaks observed at 0.1 kb and 0.5 kb. Only 2.5 % of the eccDNA in C and 2 % in HM were > 25 kb in size. The gene-rich chromosomes contributed to more number of eccDNA/Mb, while several well-known high myopia candidate genes, including catenin delta 2 (CTNND2), ubiquitin-like with PHD and ring finger domains 1 binding protein 1 like (UHRF1BP1L) , exhibited significantly increased levels of eccDNA in the anterior capsule of the lens in patients with high myopia. This study highlighted the topologic analysis of the anterior capsule of eyes with high myopia, which is an emerging direction for research and clinical applications. These findings suggested that eccDNA was commonly detected in eyes with high myopia and cataracts, and the candidate genes for high myopia identified in previous studies were also observed in the eccDNA.

2023-04-13 | GSE207646 | GEO

Whole-genome sequencing of Extrachromosomal circular DNA (eccDNA) of cerebrospinal fluid of Medulloblastoma

Project description:Background: Medulloblastoma (MB) is one of the malignant tumors of the central nervous system (CNS) with a poor prognosis and lack of effective detection. Extrachromosomal circular DNA (eccDNA) has been reported to be closely related to CNS tumors. However, there is still a gap in eccDNA of MB.Methods: Genomic features of eccDNAs were identified in MB tissues and matched cerebrospinal fluid (CSF) using a circle-map, compared with normal. The nucleotides on both sides of the eccDNAs breakpoint were analyzed to investigate the mechanisms of eccDNAs formation. Bioinformatics analysis combined with the GEO database identified reliable features of eccDNA-related genes in MB. Lasso Cox regression model, univariate and multivariate Cox regression analysis, time-dependent ROC, and Kaplan–Meier curve were used to assess the potential diagnostic and prognostic value of the Hub genes.Results: 35179 eccDNAs were identified, with the majority less than 1000 base pairs (bp). The distribution of eccDNAs on the genome was closely related to gene density. EccDNAs in CSF exhibited phase parallelism with matched MB tissues and were shown differently in tumors and normal. Ten core genes were identified in combination with GEO and showed reliable diagnostic and prognostic value in independent datasets through univariate and multivariate Cox regression. Nomogram included Hub-gene signatures was established and showed clinical benefit.Conclusions: This study described the characteristics and formation mechanism of eccDNAs in MB and CSF. The role of eccDNA in MB was revealed, and eccDNA-associated hub genes in CSF could be used as diagnostic and prognostic biomarkers for MB.

2022-10-20 | GSE205178 | GEO

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