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Multiomic analyses on the contribution of transposable elements to the cis-regulatory landscape of different types of immune cells[RNA-seq]

ABSTRACT: Transposable elements (TEs) are key contributors to genetic novelty. Despite increasing evidence of their importance, their roles in shaping the regulatory landscape of different immune cell populations remain largely unclear. Using single-cell multiome from human peripheral blood mononuclear cells, we annotated the cell-specific cis-regulatory elements for diverse immune cells and identified a highly cell-specific signature regarding overrepresented TE families. Focusing on monocytes that bear fast-evolving transcriptomes, we found that high proportions of their enhancers are TE-derived and bound by multiple pioneer transcription factors. Among them, we confirmed that the core myeloid regulator SPI1 can bind and regulate hundreds of TE-derived enhancers, which affect the expression of adjacent immune genes. Interspecies comparison reveals that non-conserved monocyte enhancers are frequently generated by lineage-specific TE insertions, and correlate with the evolved gene expression between human and mouse. Our study highlights the importance of TEs in shaping the regulatory landscape of diverse immune cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE266045 | GEO | 2025/10/21

REPOSITORIES: GEO

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Project description:Background: Transposable elements (TEs) represent a substantial fraction of the genomes, playing a major role in evolution, as sources of genetic variability. To fully appraise the role of TE in the acquisition of genetic novelty in genome evolution, we must also consider the impact of their own transcriptional activity. Results: We studied impact of TE transcriptional activity on gene using high-throughput RNA-Seq sequencing in Drosophila melanogaster. TEs, which turn out to be expressed in euchromatin as well as in heterochromatin, interact with genes at different levels. The observed transcription from TEs involve canonical or non-canonical transcription start sites (TSSs) distributed along their sequence. We also find evidences for potential bidirectional transcription from the TE promoter regions where the antisense transcript is co-opted by the host genome as TSSs of a gene. We found that active TEs seem to accumulate in the 5' upstream regions of the genes, and possibly provide an alternative transcript of the nearby gene. Indeed, predominantly, the TE transcript is collinear and overlapping the gene. Apart from the 5' upstream regions, we also found that most active TEs are transcribed on the gene transcript strand. Conversely, few transcripts from TE are anti sense with respect to the gene. This suggests that they have a disruptive action and are counter-selected. The only exceptions are for TEs located into introns, where they could provide another complex way of gene regulation, and in the 3' downstream region, where other mechanisms akin to siRNAs could take place. Finally, we noted several cases where the cryptic TSS is located on TE fragments corresponding to a low complexity sequence. Frequently these TE fragments appear to be over-represented when close to genes, suggesting a possible selected role. Conclusion: Altogether, these results suggest that active transposable elements influence host gene transcription. It is likely that some features of transposable elements have been exaptated in order to enrich the genes repertoire by opening routes to sub- or neo-functionalization. Examination of the transcription produced by transposable elements in D. melanogaster

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Multiomic analyses on the contribution of transposable elements to the cis-regulatory landscape of different types of immune cells[RNA-seq]

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