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Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells [ChIP-seq]

ABSTRACT: Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells [ChIP-seq]

PROVIDER: PRJNA506706 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8239490.fastq.gz	Fastqsanger.gz
	SRR8239491.fastq.gz	Fastqsanger.gz
	SRR8239488.fastq.gz	Fastqsanger.gz
	SRR8239489.fastq.gz	Fastqsanger.gz

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Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells

Project description:Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells

| PRJNA506704 | ENA

Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells [RNA-seq]

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Functional evaluation of transposable elements as transcriptional enhancers in mouse embryonic and trophoblast stem cells [ChIP-seq]

Project description:Transposable elements (TEs) appear to have contributed to the evolution of tissue-specific gene regulatory networks in contexts such as early development, pregnancy and innate immunity, amongst others. In mouse embryonic stem cells (ESCs), TE families such as RLTR13D6 bind key pluripotency-associated transcription factors and are enriched for histone marks that are characteristic of distal enhancers. However, it remains unclear to what extent such lineage-specific TEs are important for maintaining gene expression programmes during preimplantation development. Here we have tested the gene regulatory function of RLTR13D6 elements in ESCs using epigenetic editing approaches. Whilst we identify some elements that are important to drive gene expression, these constitute a minority of all the putative TE-derived enhancers identified through epigenomic analyses, highlighting the importance of functional tests when assessing the contribution of TEs to gene regulatory networks.

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Transposable elements as lineage-specific enhancers in endodermal-lineage cancers

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Functional evaluation of transposable elements as enhancers in mouse embryonic and trophoblast stem cells.

Project description:Transposable elements (TEs) are thought to have helped establish gene regulatory networks. Both the embryonic and extraembryonic lineages of the early mouse embryo have seemingly co-opted TEs as enhancers, but there is little evidence that they play significant roles in gene regulation. Here we tested a set of long terminal repeat TE families for roles as enhancers in mouse embryonic and trophoblast stem cells. Epigenomic and transcriptomic data suggested that a large number of TEs helped to establish tissue-specific gene expression programmes. Genetic editing of individual TEs confirmed a subset of these regulatory relationships. However, a wider survey via CRISPR interference of RLTR13D6 elements in embryonic stem cells revealed that only a minority play significant roles in gene regulation. Our results suggest that a subset of TEs are important for gene regulation in early mouse development, and highlight the importance of functional experiments when evaluating gene regulatory roles of TEs.

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Transposable elements as lineage-specific enhancers in endodermal-lineage cancers [NaNoME-seq]

Project description:Transposable elements (TE) are repetitive genomic elements that harbor binding sites for human transcription factors (TF). A regulatory role for TEs has been suggested in embryonal development and diseases such as cancer but systematic investigation of their functions has been limited by their widespread silencing in the genome. Here, we have utilized unbiased massively parallel reporter assay data using whole human genome library to identify TEs with functional enhancer activity in two human cancer types of endodermal lineage, colorectal and liver cancers. We show that the identified TE enhancers are characterized by genomic features associated with active enhancers, such as epigenetic marks and TF binding. Importantly, we identified distinct TE subfamilies that function as tissue-specific enhancers, namely MER11- and LTR12-elements in colon and liver cancers, respectively. These elements are bound by distinct TFs in each cell type, and they have predicted associations to differentially expressed genes. In conclusion, these data demonstrate how different cancer types can utilize distinct TEs as tissue-specific enhancers.

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