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Locus-specific chromatin profiling of evolutionarily young transposable elements

ABSTRACT: Locus-specific chromatin profiling of evolutionarily young transposable elements

PROVIDER: PRJNA755717 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15503416_1.fastq.gz	Fastqsanger.gz
	SRR15503416_2.fastq.gz	Fastqsanger.gz
	SRR15503417_1.fastq.gz	Fastqsanger.gz
	SRR15503417_2.fastq.gz	Fastqsanger.gz
	SRR15503418_1.fastq.gz	Fastqsanger.gz

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Locus-specific chromatin profiling of evolutionarily young transposable elements [HiChIP]

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Locus-specific chromatin profiling of evolutionarily young transposable elements [HiChIP]

Project description:Despite a vast expansion in the availability of epigenomic data, our knowledge of the chromatin landscape at interspersed repeats remains highly limited by difficulties in mapping short-read sequencing data to these regions. In particular, little is known about the locus-specific regulation of evolutionarily young transposable elements (TEs), which have been implicated in genome stability, gene regulation and innate immunity in a variety of developmental and disease contexts. Here we propose an approach for generating locus-specific protein-DNA binding profiles at interspersed repeats, which leverages information on the spatial proximity between repetitive and non-repetitive genomic regions. We demonstrate that the combination of Hi-ChIP and a newly developed mapping tool (PAtChER) yields accurate protein enrichment profiles at individual repetitive loci. Using this approach, we show that young TEs display locus- and tissue-specific chromatin profiles in both mice and humans. Insights gained using our method will be invaluable for dissecting the molecular determinants of TE regulation and their impact on the genome.

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Drug-tolerant cancer cell persisters survive lethal exposures by silencing transposable elements [ChIP-Seq]

Project description:Establishing and maintaining phenotypic heterogeneity within cell and organismal populations is an evolutionarily conserved strategy that ensures survival of the population following stressful exposures. We previously identified a transient, reversible, drug-tolerant cancer cell subpopulation that survives otherwise lethal drug exposures. Here we show that these drug-tolerant persisters (DTPs) assume a highly heterochromatic state, which requires factors that modify or bind trimethylated H3 lysine 9 (H3K9me3). The increased H3K9me3 in DTPs is largely restricted to evolutionarily young Long Interspersed Repeat elements (LINEs). This transcriptionally repressive state, which decreases the expression of these retrotransposable elements, is critical for DTP survival, and disruption of this heterochromatic state results in re-expression of LINE elements and ablation of this subpopulation. Together, these findings establish a role for epigenetic silencing of transposable elements as a population survival strategy to maintain genomic integrity in subpopulations of cancer cells during lethal drug exposures.

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Project description:Circular RNAs (circRNAs) are found across eukaryotes and can function in post-transcriptional gene regulation. Their biogenesis through a circle-forming backsplicing reaction is facilitated by reverse-complementary repetitive sequences promoting pre-mRNA folding. Orthologous genes from which circRNAs arise, overall contain more strongly conserved splice sites and exons than other genes, yet it remains unclear to what extent this conservation reflects purifying selection acting on the circRNAs themselves. Our analyses of circRNA repertoires from five species representing three mammalian lineages (marsupials, eutherians: rodents, primates) reveal that surprisingly few circRNAs arise from orthologous exonic loci across all species. Even the circRNAs from orthologous loci are associated with young, recently active and species-specific transposable elements, rather than with common, ancient transposon integration events. These observations suggest that many circRNAs emerged convergently during evolution - as a byproduct of splicing in orthologs prone to transposon insertion. Overall, our findings argue against widespread functional circRNA conservation.

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