Silencing Of Transposable Elements May Not Be A Major Driver Of Regulatory Evolution In Primate Induced Pluripotent Stem Cells

Abstract

Transposable elements (TEs) comprise a substantial proportion of primate genomes. The regulatory potential of TEs can result in deleterious effects, especially during development. It has been suggested that, in pluripotent stem cells, TEs are targeted for silencing by KRAB-ZNF proteins, which recruit the TRIM28-SETDB1 complex, to deposit the repressive histone modification H3K9me3. TEs, in turn, can acquire mutations that allow them to evade detection by the host, and hence KRAB-ZNF proteins need to rapidly evolve to counteract them. To investigate the short-term evolution of TE silencing, we profiled the genome-wide distribution of H3K9me3 in induced pluripotent stem cells from ten human and seven chimpanzee individuals. We performed chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) for H3K9me3, as well as total RNA sequencing. We focused specifically on cross-species H3K9me3 ChIP-seq data that mapped to four million orthologous TEs. We found that, depending on the TE class, 10-60% of elements are marked by H3K9me3, with SVA, LTR and LINE elements marked most frequently. We found little evidence of inter-species differences in TE silencing, with as many as 80% of orthologous, putatively silenced, TEs marked at similar levels in humans and chimpanzees. Our data suggest limited species-specificity of TE silencing across six million years of primate evolution. Interestingly, the minority of TEs enriched for H3K9me3 in one species are not more likely to be associated with gene expression divergence of nearby orthologous genes. We conclude that orthologous TEs may not play a major role in driving gene regulatory divergence between humans and chimpanzees.