DHX36-mediated G-quadruplexes unwinding is essential for oocyte and early embryo development in mice

The role of G-quadruplex (G4) structures and their effects on oocyte and early embryo development remain unclear. We discovered that the G4 helicase DHX36 is essential for oocyte growth and the maternal-to-zygotic transition (MZT). Conditional knockout of DHX36 resulted in DNA G4 accumulation in mouse oocytes, reducing chromatin accessibility, and inhibiting RNA transcription, ultimately disrupting transcriptome homeostasis during oocyte growth and MZT. We performed Smart-seq2 on samples from wild-type (WT) and DHX36 conditional knockout (CKO) female mice, including growing oocytes (2-week-old), fully-grown oocytes (3-week-old and 4-week-old), metaphase II oocytes (3-week-old), and zygotes (3-week-old).G-四链体（G-quadruplex，G4）结构的生物学功能及其对卵母细胞与早期胚胎发育的影响目前仍未明确。本研究发现，G4解旋酶DHX36是卵母细胞生长及母源-合子转换（maternal-to-zygotic transition, MZT）过程的必需因子。对DHX36进行条件性敲除，会导致小鼠卵母细胞内DNA G4结构蓄积，降低染色质开放度并抑制RNA转录，最终破坏卵母细胞生长及MZT过程中的转录组稳态。我们对野生型（wild-type, WT）与DHX36条件性敲除（conditional knockout, CKO）雌性小鼠的多类样本开展了Smart-seq2测序，样本涵盖生长阶段卵母细胞（2周龄）、完全成熟卵母细胞（3周龄与4周龄）、中期II卵母细胞（3周龄）以及合子（3周龄）。