YTHDF2 promotes DNA damage repair by positively regulating the histone methyltransferase SETDB1 in spermatogonia

we reported that in the absence of YTHDF2, spermatogonia showed significantly enhanced sensitivity to etoposide and promoted apoptosis, demonstrating that the importance of YTHDF2 in the etoposide-responsive DNA damage response (DDR). Multiple modifications involved in the DDR, some of which recruit repair factors to the sites of DNA damage. N6-methyladenosine (m6A) as a crucial component of the DNA damage repair system responding to DNA lesions. Meanwhile, H3K9me3 has been implicated in DDR, which provides site for DDR factors binding to DNA lesion. Importantly, ablation of Ythdf2 reduced SETDB1 and H3K9me3 levels, and SETDB1 overexpression qualitatively suppressed the DNA damage associated with YTHDF2 loss. transcriptome analysis of GC1 spermatagonia cells; 3 replicates each: WT, Ythdf2-ko, Ythdf2-ko-OE-CTR, Ythdf2-koOE-setdb1