Cooperation between NSPc1 and DNA methylation represses HOXA11 expression and promotes apoptosis of trophoblast cells during preeclampsia  

作　　者：Lin Xie Ning Ding Siqi Sheng Honghong Zhang He Yin Lina Gao Hui Zhang Shengchao Ma Anning Yang Guizhong Li Yun Jiao Qing Shi Yideng Jiang Huiping Zhang 

机构地区：[1]NHC Key Laboratory of Metabolic Cardiovascular Diseases Research,Ningxia Medical University,Yinchuan 750004,China [2]Department of Medical Genetics,Maternal and Child Health of Hunan Province,Changsha 410008,China [3]Ningxia Key Laboratory of Vascular Injury and Repair Research,Ningxia Medical University,Yinchuan 750004,China [4]School of Basic Medical Sciences,Ningxia Medical University,Yinchuan 750004,China [5]Department of Clinical Medicine,Ningxia Medical University,Yinchuan 750004,China [6]General Hospital of Ningxia Medical University,Yinchuan 750004,China [7]Department of Infectious Diseases,General Hospital of Ningxia Medical University,Yinchuan 750004,China [8]Department of Gynecology,General Hospital of Ningxia Medical University,Yinchuan 750004,China

出　　处：《Acta Biochimica et Biophysica Sinica》2023年第2期202-214,共13页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.U21A20343,82171682,and 82270492);the Natural Science Foundation of Ningxia Hui Autonomous Region(No.2020AAC02038);the Key Research and Development Projects in Ningxia Hui Autonomous Region(Nos.2019BFG02004,2021BEG02028,2020BEG03005,2020BFH02003,and 2022BEG02054);the Basic Scientific Research Operating Expenses from the public welfare research institutes at the central level of the Chinese Academy of Medical Sciences(No.2019PT330002).

摘　　要：Accumulating evidence has shown that the apoptosis of trophoblast cells plays an important role in the pathogenesis of preeclampsia,and an intricate interplay between DNA methylation and polycomb group(PcG)proteinmediated gene silencing has been highlighted recently.Here,we provide evidence that the expression of nervous system polycomb 1(NSPc1),a BMI1 homologous polycomb protein,is significantly elevated in trophoblast cells during preeclampsia,which accelerates trophoblast cell apoptosis.Since NSPc1 acts predominantly as a transcriptional inactivator that specifically represses HOXA11 expression in trophoblast cells during preeclampsia,we further show that NSPc1 is required for DNMT3a recruitment and maintenance of the DNA methylation in the HOXA11 promoter in trophoblast cells during preeclampsia.In addition,we find that the interplay of DNMT3a and NSPc1 represses the expression of HOXA11 and promotes trophoblast cell apoptosis.Taken together,these results indicate that the cooperation between NSPc1 and DNMT3a reduces HOXA11 expression in preeclampsia pathophysiology,which provides novel therapeutic approaches for targeted inhibition of trophoblast cell apoptosis during preeclampsia pathogenesis.

关 键 词：PREECLAMPSIA nervous system polycomb 1 DNA methyltransferase 3a HOXA11 apoptosis 

分 类 号：R714.245[医药卫生—妇产科学]