LATS1控制CTCF染色体占用率和3D培养的乳腺癌细胞的荷尔蒙反应
Julieta Ramírez-Cuéllar1,2, Roberto Ferrari1,3, Rosario T Sanz4
1Center for Genomic Regulation (CRG), Barcelona Institute for Science and Technology (BIST) Barcelona, Barcelona, Spain.
The EMBO journal
|April 2, 2024
概括
与传统的二维方法相比,三维 (3D) 乳腺癌细胞培养改变了染色质结构和基因表达. 这种3D环境影响表观遗传调节,影响激素驱动的基因活性.
科学领域:
- 癌症生物学 癌症生物学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 细胞微环境是细胞微环境.
背景情况:
- 传统的癌症表观基因组研究使用二维细胞培养.
- 细胞外矩阵和3D环境显著影响细胞功能.
- 了解3D效应对于癌症研究至关重要.
研究的目的:
- 研究2D和3D培养T47D乳腺癌细胞之间的物理,生化和基因组差异.
- 阐明3D细胞行为背后的表观遗传机制.
- 探索Hippo通路和CTCF在3D染色体组织中的作用.
主要方法:
- 在2D单层和3D球形中培养T47D乳腺癌细胞.
- 分析核形态和染色质的可访问性.
- 基因表达概况. 基因表达概况.
- 对染色质构成的Hi-C分析.
- 西方涂抹和免疫光用于蛋白质分析.
主要成果:
- 三维球形图显示了具有紧色素的圆形核.
- ~2000个基因在3D中表现出改变的表达,其中大多数被抑制.
- Hi-C显示了B区的丰富,CTCF结合的减少,以及3D中TAD融合的增加.
- 河马通路激活 (LATS1激酶) 会导致CTCF的移位和TAD的融合.
- 在3D中增加的孕激素受体 (PR) 结合增强了激素调节的基因表达.
结论:
- 3D环境深刻地改变了乳腺癌细胞表观基因组和染色体结构.
- 河马通路信号和CTCF动态是3D染色体组织的关键调节者.
- 3D培养增强激素受体活性,影响乳腺癌细胞中的基因调节.
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