2. Academic Validation
  3. PR-SET7 epigenetically restrains uterine interferon response and cell death governing proper postnatal stromal development

PR-SET7 epigenetically restrains uterine interferon response and cell death governing proper postnatal stromal development

  • Nat Commun. 2024 Jun 10;15(1):4920. doi: 10.1038/s41467-024-49342-6.
Haili Bao # 1,  Yang Sun # 1,  Na Deng # 1,  Leilei Zhang 1,  Yuanyuan Jia 1,  Gaizhen Li 1,  Yun Gao 1,  Xinyi Li 1,  Yedong Tang 1,  Han Cai 1,  Jinhua Lu 1,  Haibin Wang 2 3,  Wenbo Deng 4,  Shuangbo Kong 5
Affiliations

Affiliations

  • 1 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
  • 2 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. haibin.wang@vip.163.com.
  • 3 State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. haibin.wang@vip.163.com.
  • 4 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. wbdeng@xmu.edu.cn.
  • 5 Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China. shuangbo_kong@163.com.
  • # Contributed equally.
PMID: 38858353 DOI: 10.1038/s41467-024-49342-6
Abstract

The differentiation of the stroma is a hallmark event during postnatal uterine development. However, the spatiotemporal changes that occur during this process and the underlying regulatory mechanisms remain elusive. Here, we comprehensively delineated the dynamic development of the neonatal uterus at single-cell resolution and characterized two distinct stromal subpopulations, inner and outer stroma. Furthermore, single-cell RNA Sequencing revealed that uterine ablation of Pr-set7, the sole methyltransferase catalyzing H4K20me1, led to a reduced proportion of the inner stroma due to massive cell death, thus impeding uterine development. By combining RNA Sequencing and epigenetic profiling of H4K20me1, we demonstrated that PR-SET7-H4K20me1 either directly repressed the transcription of interferon stimulated genes or indirectly restricted the interferon response via silencing endogenous retroviruses. Declined H4K20me1 level caused viral mimicry responses and ZBP1-mediated Apoptosis and Necroptosis in stromal cells. Collectively, our study provides insight into the epigenetic machinery governing postnatal uterine stromal development mediated by PR-SET7.

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