2. Academic Validation
  3. Ethionine-induced S-adenosylmethionine deficiency suppressed H3K27me3 and cell differentiation during neural tube development in mice

Ethionine-induced S-adenosylmethionine deficiency suppressed H3K27me3 and cell differentiation during neural tube development in mice

  • J Cell Physiol. 2024 Oct 6:e31452. doi: 10.1002/jcp.31452.
Li Zhang 1 2 3,  Xiaona Zhang 2,  Yurong Liu 2,  Kaixin Wei 2,  Huijing Ma 4,  Li Xia 4,  Rui Cao 2,  Yuqing Sun 1,  Ronghua Zheng 5,  Xiuwei Wang 6,  Bingmei Chang 2
Affiliations

Affiliations

  • 1 Department of Hepatobiliary and Pancreatic Surgery and Liver Transplant Center, The First Hospital of Shanxi Medical University, Taiyuan, China.
  • 2 Department of Biochemistry and Molecular Biology, Shanxi Medical University, Taiyuan, China.
  • 3 Key Laboratory of Digestive Diseases and Organ Transplantation, Institute of Liver Diseases and Organ Transplantation, Shanxi Medical University, Taiyuan, China.
  • 4 Department of Pediatrics, The First Hospital of Shanxi Medical University, Taiyuan, China.
  • 5 Department of Medicine, Linfen Vocational and Technical College, Linfen, China.
  • 6 Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, Beijing, China.
PMID: 39370687 DOI: 10.1002/jcp.31452
Abstract

S-adenosylmethionine (SAM) as a major methyl donor plays a key role in methylation modification in vivo, and its disorder was closely related to neural tube defects (NTDs). However, the exact mechanism between SAM deficiency and NTDs remained unclearly. Hence, we investigated the association between histone methylation modification and cell differentiation in NTDs mice induced by SAM deficiency. The levels of SAM and SAH (S-adenosylhomocysteine) were determined by Enzyme linked immunosorbent assay (ELISA). The level of histone methylation, β-catenin were analyzed by Western blot, reversing transcription and quantitative PCR (RT-qPCR) and immunofluorescence. The results showed that the incidence rate of NTDs induced by ethionine were 46.2%. Post treatment of ethionine combined with SAM, the incidence rate of NTDs was reduced to 26.2%. The level of SAM was significantly decreased (p < 0.05) and a reduction in the SAM/SAH ratio was observed after entionine treatment. The SAM deficiency caused the reduction of H3K27me3 modifications and the elevated UTX activity (p < 0.05), and inhibited the expressions of β-catenin. The differentiations of NSCs into neurons and oligodendrocytes were inhibited under SAM deficiency (p < 0.05). These results indicated that the SAM deficiency led to reduce H3K27me3 modifications, prevented the β-catenin signaling pathway and NSCs differentiation, which provided an understanding of the novel function of epigenetic regulation in NTDs.

Keywords

H3K27me3; S‐adenosylmethionine; differentiation; neural stem cells; neural tube defects.

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