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

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.