Abstract
Approximately half of the human genome consists of mobile repetitive DNA sequences known as transposable elements (TEs). They are usually silenced by epigenetic mechanisms, but a few are known to escape silencing at embryonic stages, affecting early human development by regulating nearby protein-coding genes. To investigate transcriptional activity in human adult tissues we systematically investigate the expression landscape of about 4.2 million non-coding TEs in 8,051 RNA-Seq datasets from up to 49 adult tissues and 540 individuals. We show that approximately 79,558 individual TEs (2%). belonging to 856 subfamilies escape epigenetic silencing in adult tissues and become transcriptionally active, often in a very tissue-specific manner. Supporting a role for TEs in the regulation of expression of nearby genes, we found the expression of TEs often correlated with the expression of nearby genes, and significantly stronger when the TEs include eQTLs for the genes. We identified thousands of tissue-elevated, sex-associated TEs in the breast, ethnicity-associated in the skin and age-associated in the tibial artery, where we found a potential implication of two TE subfamilies in atherosclerosis. Our results suggest a functional role of TEs in the regulation of gene expression, support their implication in human phenotypes, and also serve as a comprehensive resource of transcriptionally active TEs in human adult tissues.
