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2021医学院短学期系列讲座(六)

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Peter Reinach

温州医科大学

教授

Changes in histone methyl transferase   activity alter corneal epithelial wound healing via modulating   H3K9me3-histone mediated repression of p27

722

9:30-11:30

线上

专家简介:

厦门大学讲座教授,纽约州立大学(State University of New York)视光学院普通药理学和生物科学教授,哥伦比亚大学(ColumbiaUniversity)眼科客座教授,生理和细胞生物学客座教授。长期从事角膜生理学研究,在角膜上皮细胞信号传导通路及离子通道研究方面卓有建树,在国际知名杂志发表论文100余篇。

内容简介:

Corneal epithelial wound healing (CEWH) is essential for maintaining the integrity and barrier function of this tissue. Although histone modifications mediating gene expression patterns are fundamental in some other tissues, it remains unclear whether these gene regulation patterns underlie CEWH. Here, this question is addressed by providing a comprehensive signature of epigenetic modifiers involved in CEWH. NanoString nCounter technology identified ninety-two differentially expressed epigenetic modifiers during CEWH. One of the upregulated epigenetic modifiers, suppressor of variegation 3-9 homolog 1 (SUV39H1) attracted our interest because it plays a vital role in mediating gene silencing via histone H3 trimethylation of lysine 9 (H3K9me3). Firstly, Suv39h1 was confirmed to be upregulated in response to corneal injury. Its downregulation significantly inhibited human corneal epithelial cell (HCEC) proliferation and retarded in vivo CEWH. Furthermore, knockdown of SUV39H1 upregulated p27 expression level and reduced H3K9me3 marks at p27 promoter in HCECs. Conversely, p27 was remarkably downregulated with elevated H3K9me3 marks at its promoter during in vivo CEWH. In conclusion, SUV39H1 plays a critical role in regulating corneal epithelial cell proliferation via H3K9me3-mediated suppression of p27 during CEWH.  These findings suggest that epigenetic modifiers such as SUV39H1can serve as targets to improve therapeutic management of corneal epithelial repair in a clinical setting.