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Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci

ABSTRACT: Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci

PROVIDER: PRJNA967669 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR24446410_1.fastq.gz	Fastqsanger.gz
	SRR24446410_2.fastq.gz	Fastqsanger.gz
	SRR24446411_1.fastq.gz	Fastqsanger.gz
	SRR24446411_2.fastq.gz	Fastqsanger.gz
	SRR24446412_1.fastq.gz	Fastqsanger.gz

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Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci [WGBS]

Project description:Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci [WGBS]

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Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci [WGBS]

Project description:Transposable elements (TEs) are typically silenced by DNA methylation and repressive histone modifications in differentiated healthy human tissues. However, TE expression increases in a wide range of cancers and is correlated with global hypomethylation of cancer genomes. We assessed expression and DNA methylation of TEs in fibroblast cells that were serially transduced with hTERT, SV40, and HRASR24C to immortalize and then transform them, which models the different steps of the tumorigenesis process. RNA-sequencing and whole-genome bisulfite sequencing were performed at each stage of transformation. TE expression significantly increased as cells progressed through transformation, with the largest increase in expression after the final stage of transformation, consistent with data from human tumors. The upregulated TEs were dominated by endogenous retroviruses (LTRs). Most differentially methylated regions (DMRs) in all stages were hypomethylated, with the greatest hypomethylation in the final stage of transformation. A majority of the DMRs overlapped TEs from the RepeatMasker database, indicating that TEs are preferentially demethylated. Many hypomethylated TEs displayed a concordant increase in expression. Demethylation began during immortalization and continued into transformation, while upregulation of TE transcription occurred in transformation. Numerous LTR elements upregulated in the model were also identified in TCGA datasets of breast, colon, and prostate cancer. Overall, these findings indicate that transposable elements, specifically endogenous retroviruses, are demethylated and transcribed during transformation.

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Small RNA accumulation in Transposable Element-silent and Transposable Element-active epigenomes

Project description:Background: The small RNAs that Transposable Elements generate are vastly different when they are transcriptionally silenced compared to when they are transcriptionally activated. We performed the deep sequencing of small RNAs in a number of small RNA biogenesis mutants in both Transposable Element-silenced and Transposable Element-active epigenome backgrounds. Results: We found that Transposable Elements generate large amounts of 21-22nt siRNAs only when they are transcriptionally active. These 21-22nt siRNAs are incorporated into the AGO6 protein. Conclusion: Ago6 is the key protein that bridges the post-transcriptional degradation of Transposable Element mRNAs and the establishment of DNA methylation. Examination of flower bud small RNAs from wild type and 5 single or double mutant combinations, many of which have biological replicates. In addition, IP purification of the AGO6 protein (and mock no-antigen controls) followed by sequencing of the incorporated small RNAs. Replicate A for Col and ddm1 are submitted in GSE41755

2014-11-14 | E-GEOD-57191 | biostudies-arrayexpress

Small RNA accumulation in Transposable Element-silent and Transposable Element-active epigenomes

2014-11-14 | GSE57191 | GEO

Malignant Transformation Drives DNA Methylation Loss and Transcriptional Activation of Transposable Element Loci

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-06-27 | GSE231780 | GEO

Incorporation of transposable element small RNAs into the Arabidopsis AGO1 protein

Project description:Background: Transposable element 24 nucleotide small RNAs are not efficiently incorporated into the AGO1 protein, which is involved in endogenous RNAi and gene regulation through the microRNA and tasiRNA pathways. Results: The AGO1 protein incorporates large quantities of transposable element siRNAs when transposable elements are epigenetically activated and transcribed. The incorporation of transposable element siRNAs is at the expense of the most abundant microRNAs. These transposable element siRNAs can act as tasiRNAs, regulating genes that they have partial complementarity to. Conclusion: Transposable element small RNAs are more dynamic than previously thought. They can be incorporated into AGO1 and regulate genes. Three biological replicates of small RNA sequencing from two genotypes

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Transposable Elements Lose Methylation and Gain Expression During Malignant Transformation [RNA-seq]

Project description:Transposable Elements Lose Methylation and Gain Expression During Malignant Transformation [RNA-seq]

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Oncogenic Transformation Drives DNA Methylation Loss and Transcriptional Activation at Transposable Element Loci.

Project description:Transposable elements (TE) are typically silenced by DNA methylation and repressive histone modifications in differentiated healthy human tissues. However, TE expression increases in a wide range of cancers and is correlated with global hypomethylation of cancer genomes. We assessed expression and DNA methylation of TEs in fibroblast cells that were serially transduced with hTERT, SV40, and HRASR24C to immortalize and then transform them, modeling the different steps of the tumorigenesis process. RNA sequencing and whole-genome bisulfite sequencing were performed at each stage of transformation. TE expression significantly increased as cells progressed through transformation, with the largest increase in expression after the final stage of transformation, consistent with data from human tumors. The upregulated TEs were dominated by endogenous retroviruses [long terminal repeats (LTR)]. Most differentially methylated regions (DMR) in all stages were hypomethylated, with the greatest hypomethylation in the final stage of transformation. A majority of the DMRs overlapped TEs from the RepeatMasker database, indicating that TEs are preferentially demethylated. Many hypomethylated TEs displayed a concordant increase in expression. Demethylation began during immortalization and continued into transformation, while upregulation of TE transcription occurred in transformation. Numerous LTR elements upregulated in the model were also identified in The Cancer Genome Atlas datasets of breast, colon, and prostate cancer. Overall, these findings indicate that TEs, specifically endogenous retroviruses, are demethylated and transcribed during transformation.SignificanceAnalysis of epigenetic and transcriptional changes in a transformation model reveals that transposable element expression and methylation are dysregulated during oncogenic transformation.

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Epigenomic conservation of transposable element silencing

Project description:Epigenomic conservation of transposable element silencing

| PRJNA379439 | ENA

Incorporation of transposable element small RNAs into the Arabidopsis AGO1 protein

2014-04-07 | GSE45990 | GEO