PKM2-induced histone lactylation drives chromatin conformation changes in PCOS
Release date:
2025-10-13
Description:
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder among women of reproductive age. While metabolic dysfunction is a central feature of PCOS, the precise mechanisms driving its pathogenesis remain elusive. In this study, we uncover a novel feedback loop involving androgen, PKM2, and histone lactylation in granulosa cells (GCs) that underlies PCOS development. Our findings reveal that PKM2-mediated nuclear translocation triggers histone lactylation modifications on H3K9 and H3K18, leading to alterations in three-dimensional genome organization near crucial androgen synthesis genes such as CYP11A1 and CYP17A1. This cascade establishes a positive feedback loop that amplifies the expression of PCOS-related genes. In conclusion, our study highlights the potential therapeutic value of disrupting the androgen-PKM2-chromatin-conformation feedback loop as a promising strategy for treating PCOS.
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