CTCF orchestrated enhancer hijacking accelerated tumorigenesis through remodeling 3D chromosomal architecture in NTS locus [ChIP-seq]

We identified aberrant CTCF binding lead to a 3D chromosomal interactional driver in NTS locus that accelerates tumorigenesis of uveal melanoma. Both enhancer deletion and abolishing CTCF binding lead to the loss of chromosomal looping and triggered therapeutic efficacy in inhibiting tumorigenesis. Our study shed light on a functional chromosomal architecture induced enhancer hijacking, thereby provide novel concept of 3D-chromosomal conformation exploration. Overall design: We performed CTCF ChIP-Seq in melanoma cells and RNA-seq in 2 types of ocular melanoma cells with or without NTS promoter deletion

本研究发现，异常的CCCTC结合因子（CTCF）结合可在神经降压素（NTS）基因座形成三维染色体互作驱动因子，进而加速葡萄膜黑色素瘤的发生发展。敲除增强子或消除CTCF结合均可导致染色体环结构丢失，并在抑制肿瘤发生过程中发挥治疗功效。本研究阐明了功能性染色体结构诱导的增强子劫持现象，从而为三维染色体构象的探索提供了全新的研究思路。
实验设计：本研究在黑色素瘤细胞中开展了CTCF染色质免疫共沉淀测序（ChIP-Seq）实验，并在两种分别带有或缺失NTS启动子的眼部黑色素瘤细胞中进行了转录组测序（RNA-seq）。