Tracking mobilization uncovers an evolutionarily conserved mechanism in suppressing mobile genetic elements [RNA-seq]

While the resurrection of transposons is tightly linked with cancer, neurodegenerative disorder and other pathologies, the precise suppression mechanisms and mobilization events of transposons during somatic development remain largely obscure. Here, we present a highly conserved mechanism that prevents transposon activation and mobilization. By tracking transposition events, we identified that Cramp1 plays a pivotal role in safeguarding both Drosophila and mouse development through silencing transposon mobility. Cramp1 was characterized as a major factor that specifically binds to the DNA sequences of histone gene cluster through its SANT domain, thereby initiating his1 transcription. The linker protein H1 then physically interacts and recruits Nsd to catalyze H3K36 dimethylation, which subsequently promotes proper deposition of both H4K20m3 and H3K9me3 to H3K36me2 established heterochromatin region for transposon silencing. In the absence of Cramp1 protection, uncontrolled transposons will induce massive DNA breaks, leading to abnormal hindgut regeneration in Drosophila and disrupted embryonic erythropoiesis in mice. Our finding highlights the endless arms race between hosts and transposons happening during evolution, wherein the key factors also evolve to suppress transposon mobilizations during somatic development.