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

Haili Bao, Yang Sun, Na Deng, Leilei Zhang, Yuanyuan Jia, Gaizhen Li, Yun Gao, Xinyi Li, Yedong Tang, Han Cai, Jinhua Lu, Haibin Wang (), Wenbo Deng () and Shuangbo Kong ()
Additional contact information
Haili Bao: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Yang Sun: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Na Deng: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Leilei Zhang: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Yuanyuan Jia: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Gaizhen Li: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Yun Gao: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Xinyi Li: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Yedong Tang: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Han Cai: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Jinhua Lu: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Haibin Wang: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Wenbo Deng: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen
Shuangbo Kong: The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-49342-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49342-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-49342-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().