Lu Yiming, Shan Guangyu, Xue Jiguo, Chen Changsheng, Zhang Chenggang
Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China.
Department of Health Statistics, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China
Nucleic Acids Res. 2016 Jul 27;44(13):6200-12. doi: 10.1093/nar/gkw249. Epub 2016 Apr 11.
CCCTC-binding factor (CTCF) is a multi-functional protein that is assigned various, even contradictory roles in the genome. High-throughput sequencing-based technologies such as ChIP-seq and Hi-C provided us the opportunity to assess the multivalent functions of CTCF in the human genome. The location of CTCF-binding sites with respect to genomic features provides insights into the possible roles of this protein. Here we present the first genome-wide survey and characterization of three important functions of CTCF: enhancer insulator, chromatin barrier and enhancer linker. We developed a novel computational framework to discover the multivalent functions of CTCF based on chromatin state and three-dimensional chromatin architecture. We applied our method to five human cell lines and identified ∼46 000 non-redundant CTCF sites related to the three functions. Disparate effects of these functions on gene expression were found and distinct genomic features of these CTCF sites were characterized in GM12878 cells. Finally, we investigated the cell-type specificities of CTCF sites related to these functions across five cell types. Our study provides new insights into the multivalent functions of CTCF in the human genome.
CCCTC结合因子（CTCF）是一种多功能蛋白，在基因组中发挥着多种甚至相互矛盾的作用。基于高通量测序的技术，如染色质免疫沉淀测序（ChIP-seq）和高通量染色体构象捕获技术（Hi-C），为我们评估CTCF在人类基因组中的多价功能提供了机会。CTCF结合位点相对于基因组特征的位置为了解该蛋白的可能作用提供了线索。在此，我们首次对CTCF的三种重要功能进行全基因组范围的调查和表征：增强子绝缘子、染色质屏障和增强子连接子。我们开发了一种新颖的计算框架，基于染色质状态和三维染色质结构来发现CTCF的多价功能。我们将我们的方法应用于五种人类细胞系，鉴定出约46000个与这三种功能相关的非冗余CTCF位点。在GM12878细胞中发现了这些功能对基因表达的不同影响，并对这些CTCF位点的不同基因组特征进行了表征。最后，我们研究了这五种细胞类型中与这些功能相关的CTCF位点的细胞类型特异性。我们的研究为CTCF在人类基因组中的多价功能提供了新的见解。
