在人类肺上皮细胞中识别了一种调节子相互作用蛋白质基因的远端增强剂
Feng Guo1, Li Zhang2, Yuzhen Yu3
1Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Jiangsu Key Laboratory of Immunity and Metabolism, Department of Pathogenic Biology and Immunology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
EBioMedicine
|February 28, 2024
概括
一种新发现的增强剂调节人类肺细胞中的HHIP基因表达,影响慢性阻塞性肺病 (COPD) 风险. 这一发现揭示了HHIP的存在.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 肺部医学 肺部医学
背景情况:
- 显著的4q31染色体基因位点与COPD易感性和肺功能有关.
- 这个位点内的HHIP基因在人类和小鼠肺部表现出不同的表达模式,具有未知的调节机制.
- 了解HHIP调节对于阐明COPD病原性至关重要.
研究的目的:
- 在COPD 4q31 GWAS位置内识别和描述监管元素.
- 研究这些元素在调节人类肺细胞中HHIP表达中的作用.
- 在COPD的背景下探索HHIP失调的功能后果.
主要方法:
- 单核ATAC-seq (snATAC-seq) 用于绘制人类肺细胞中的开放色素区域.
- 染色体免疫沉 (ChIP),记者试验和染色体构成捕获 (3C) 试验用于分析调节元素.
- 编辑CRISPR/Cas9基因以评估远端增强剂的功能及其对HHIP表达和上皮-介质细胞转换 (EMT) 的影响.
主要成果:
- 在人类支气管上皮细胞中发现了一种调节HHIP转录的远端增强剂.
- 这种增强剂以SMAD3依赖的方式起作用,并保持在HHIP基因附近的染色质拓.
- 减少HHIP表达导致TGFβ诱导的上皮层-介质细胞转变 (EMT) 的增加.
结论:
- 远端增强剂控制在恒温条件下HHIP表达,并响应TGFβ在人类支气管上皮细胞中的信号传递.
- HHIP和TGFβ信号通路之间的相互作用可能有助于COPD的发病.
- 这项研究揭示了HHIP的新型监管机制,对COPD有影响.
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