Transposable elements function as mechanical sensors [ChIP-seq]

Transposable elements (TEs), comprising almost half of the genome, are tightly controlled by intrinsic factors. However, how TEs are modulated by extrinsic mechanical forces remains unknown. To address this question, we culture human embryonic stem cells on hydrogels with different rigidity and comprehensively analyze the changes in transcriptome, epigenome and genome architecture of TEs, and find that TEs are able to sense mechanical forces. Upon sensing changes in substrate rigidity, a majority of TEs exhibit elevated or declined transcription, accompanied by corresponding chromatin state alterations. Moreover, mechanotransducer YAP binds directly to a subset of TEs, especially LTR7/HERV-H, and its loss partly recapitulates effects of soft substrate on TEs. Notably, mechanical forces are required for TEs’ chromatin interaction through YAP and CTCF cooperation. Functionally, mechano-sensing TE-enhancer directs definitive endoderm formation through the regulation of distal target, FAM189A2. Overall, our results demonstrate that TEs are mechanical sensors, and that TE-enhancers dictate cell fate. Cells were cultured on the hydrogels with different rigidity, and were collected for RNA-seq, ChIP-seq and HiCAR.