title: Defining the multivalent functions of CTCF from chromatin state and three-dimensional chromatin interactions.
abstract: 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.
authors.affiliation: Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China.
authors.forename: Guangyu
authors.initials: G
authors.lastname: Shan
authors.affiliation: Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China.
authors.forename: Jiguo
authors.initials: J
authors.lastname: Xue
authors.affiliation: Department of Health Statistics, School of Military Preventive Medicine, Fourth Military Medical University, Xi'an 710032, China chencs@fmmu.edu.cn.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Chen
authors.affiliation: Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China zhangcglab@gmail.com.
authors.forename: Chenggang
authors.initials: C
authors.lastname: Zhang
mesh_terms: D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D019070:Cell Lineage / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D038101:Insulator Elements / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D012097:Repressor Proteins