Architectural and evolutionary features of TE-derived TSSs shape tissue-specific promoter activity in the human genome.

Abstract

Transposable elements are abundant in the human genome and have been increasingly recognized as sources of alternative promoters. Yet, the extent of their transcriptional activity in human tissues and the features that govern their regulatory potential remain unclear. Here, we integrated high-resolution RAMPAGE data from 115 human biosamples to construct a comprehensive atlas of 26,056 transcription start sites derived from transposable elements. These sites contribute to tissue-specific gene expression, with a notable fraction originating from primate- and hominid-specific elements. Transposable element-derived transcription start sites exhibit focused, narrow-peak architectures enriched for TATA boxes and depleted of CpG islands. Phylogenetic analyses reveal a continuous gradient in promoter strength and transcriptional precision across transposable element subfamilies, with evolutionarily younger elements retaining intrinsic promoter motifs that drive focused and robust transcription, whereas older, more divergent elements exhibit broader initiation patterns and lower intrinsic activity. Together, these findings advance our understanding of how the evolution and preservation of promoter features shape the capacity of transposable elements to be exapted as functional promoters, potentially contributing to lineage-specific regulatory innovation in primates.