| 项目编号 |
PRJCA027826 |
| 项目标题 |
PKM2-induced histone lactylation drives chromatin conformation changes in PCOS |
| 涉及领域 |
Medical |
| 数据类型 |
Epigenomics
Transcriptome or Gene expression
Genome sequencing
|
| 物种名称 |
Mus musculus
Homo sapiens
|
| 描述信息 |
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. By disrupting this cycle within GCs, we observe a significant reduction in hyperandrogenism and improvements in folliculogenesis in a PCOS-like animal model. 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. Importantly, pharmacological inhibition of PKM2 not only mitigates PCOS-like symptoms in mice but also restores PCOS-associated gene expression to normal levels. 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. |
| 样品范围 |
Monoisolate |
| 发布日期 |
2025-10-13 |
| 出版信息 |
| PubMed ID |
文章标题 |
杂志名称 |
Doi |
发表年份 |
| 41253762
|
Pyruvate kinase M2-mediated histone lactylation alters three-dimensional genomic architecture in polycystic ovary syndrome
|
Signal Transduction and Targeted Therapy
|
10.1038/s41392-025-02468-5
|
2025
|
|
|
| 项目资金来源 |
| 机构 |
项目类型 |
授权项目ID |
授权项目名称 |
| National Natural Science Foundation of China (NSFC)
|
|
N/A
|
|
|
|
| 提交者 |
Hongbo
Yang (hongboyang@fudan.edu.cn)
|
| 提交单位 |
Fudan University |
| 提交日期 |
2024-07-08 |
