Genome-Wide Analysis of the Association of Transposable Elements with Gene Regulation Suggests that Alu Elements Have the Largest Overall Regulatory Impact

Nearly half of the human genome is made up of transposable elements (TEs), and there is evidence that TEs are involved in gene regulation. In this study, we have integrated publicly available genomic, epigenetic, and transcriptomic data to investigate this in a genome-wide manner. A bootstrapping statistical method was applied to minimize confounder effects from different repeat types. Our results show that although most TE classes are primarily associated with reduced gene expression, Alu elements are associated with upregulated gene expression. Furthermore, Alu elements had the highest probability of any TE class contributing to regulatory regions of any type defined by chromatin state. This suggests a general model where clade-specific short interspersed elements (SINEs) may contribute more to gene regulation than ancient/ancestral TEs. Our exhaustive analysis has extended and updated our understanding of TEs in terms of their global impact on gene regulation and suggests that the most recently derived types of TEs, that is, clade- or species-specific SINES, have the greatest overall impact on gene regulation.