通过CTCF和H3K27甲基化调节胆固醇生物合成,对于细胞迁移至关重要
Lukasz Stanislaw Kaczmarczyk1, Dagmawit Babele1, Nehora Levi1
1Department of Molecular Biology, Faculty of Life Sciences and Ariel Center for Applied Cancer Research, Ariel University, Ariel 40700, Israel.
European journal of cell biology
|September 4, 2024
概括
通过增加胆固醇合成,CTCF (CCCTC结合因子) 的损失会损害黑色素瘤细胞迁移. 抑制胆固醇恢复了迁移,揭示了CTCF.
科学领域:
- 分子生物学分子生物学
- 癌症研究 癌症研究
- 细胞生物学 细胞生物学
背景情况:
- CTCF (CCCTC-结合因子) 对3D染色体组织和基因调节至关重要.
- 它在癌细胞迁移中的作用尚未完全理解.
- CTCF通过需要阐明的机制影响细胞迁移.
研究的目的:
- 研究CTCF影响癌细胞迁移的机制.
- 为了识别黑色素瘤细胞中由CTCF调节的分子通路.
- 了解CTCF在胆固醇生物合成中的作用及其对细胞运动性的影响.
主要方法:
- 在CTCF中利用了部分功能丧失 (pLoF) 的小鼠黑色素瘤细胞.
- 评估细胞迁移率和迁移体的形成.
- 量化胆固醇生物合成酶表达和细胞胆固醇水平.
- 分析了CTCF结合,PRC2招募和H3K27me3沉积在Hmgcs1促进体.
主要成果:
- CTCF pLoF显著抑制了黑色素瘤细胞迁移.
- 失去CTCF导致胆固醇生物合成酶的表达增加和细胞胆固醇的升高.
- 在CTCF pLoF细胞中观察到减少的迁移体形成,这表明膜动态发生了变化.
- 抑制胆固醇合成挽救了CTCF pLoF细胞中的迁移速率和迁移体形成.
- 发现CTCF可以防止促进子循环并通过PRC2和H3K27me3抑制Hmgcs1转录,从而限制SREBP2结合.
结论:
- CTCF抑制胆固醇生物合成,以支持黑色素瘤细胞迁移.
- CTCF通过涉及PRC2和H3K27me3.3的表观遗传机制调节Hmgcs1的转录.
- CTCF作为胆固醇生物合成的新型调节剂,对胆固醇相关疾病有影响.
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