特雷姆2
YY1年
转录因子
小胶质细胞
生物
抄写(语言学)
基因沉默
受体
癌症研究
荧光素酶
基因
发起人
基因表达
分子生物学
细胞生物学
免疫学
遗传学
转染
炎症
语言学
哲学
作者
Yanhui Lu,Xin Huang,W. Liang,Yu Liu,Mengen Xing,Wenhao Pan,Yun Zhang,Zhe Wang,Weihong Song
标识
DOI:10.1016/j.jbc.2023.104688
摘要
TREM2 encoding the transmembrane receptor protein TREM2 is a risk gene of Alzheimer's disease (AD), and the impairment of TREM2 functions in microglia due to mutations in TREM2 may significantly increase the risk of AD by promoting AD pathologies. However, how the expression of TREM2 is regulated and the transcription factors required for TREM2 expression are largely unknown. By luciferase assay, DNA pull-down, and in silico predictions, we identified Yin Yang 1(YY1) as a binding protein of the minimal promoter of the TREM2 gene, and the binding was further confirmed by EMSA and DNA pull-down assay. shRNA-mediated YY1 silencing significantly reduced the activity of the TREM2 minimal promoter and TREM2 protein levels in the microglial cell line BV2 and the neuroblastoma Neuro2A. Furthermore, we found that the levels of TREM2 and YY1 were both downregulated in lipopolysaccharide-treated BV2 cells and in the brain of AD model mice. These results demonstrated that YY1 plays a crucial role in the regulation of TREM2 expression. Our study suggests that microglial YY1 could be targeted to maintain TREM2 expression for AD prevention and therapy.
科研通智能强力驱动
Strongly Powered by AbleSci AI