Transposable elements impact the human regulatory landscape through cell type specific epigenomic associations

Abstract Transposable elements (TEs) are DNA sequences able to create copies of themselves within the genome. TEs have been shown to act as cis-regulatory elements and be co-opted in the human genome. Thus, their impact might come from their relationship with the epigenome. However, a systematic analysis that relates TEs with chromatin histone marks across human cell types remains lacking. Here we leverage a dataset from the International Human Epigenome Consortium featuring 4867 uniformly processed ChIP-seq experiments for 6 histone marks across 47 cell types and show that TEs have drastically different enrichments levels across histone marks. We find that TEs are generally depleted but enriched in select contexts such as L1s in H3K9me3 histone mark. Notably, we identify 456 cell type-histone-TE triplets with strong cell-type specific enrichments and show that many of these triplets are associated with relevant biological processes.