Systematical identification of cell-specificity of CTCF-gene binding based on epigenetic modifications

Author:

Wu Jie1,Zhang Li1,Song Qian1,Yu Lei1,Wang Shuyuan1,Zhang Bo1,Wang Weida1,Xia Peng1,Chen Xiaowen1,Xiao Yun1,Xu Chaohan1

Affiliation:

1. Bioinformatics at Harbin Medical University, China

Abstract

Abstract The CCCTC-binding factor (CTCF) mediates transcriptional regulation and implicates epigenetic modifications in cancers. However, the systematically unveiling inverse regulatory relationship between CTCF and epigenetic modifications still remains unclear, especially the mechanism by which histone modification mediates CTCF binding. Here, we developed a systematic approach to investigate how epigenetic changes affect CTCF binding. Through integration analysis of CTCF binding in 30 cell lines, we concluded that CTCF generally binds with higher intensity in normal cell lines than that in cancers, and higher intensity in genome regions closed to transcription start sites. To facilitate the better understanding of their associations, we constructed linear mixed-effect models to analyze the effects of the epigenetic modifications on CTCF binding in four cancer cell lines and six normal cell lines, and identified seven epigenetic modifications as potential epigenetic patterns that influence CTCF binding intensity in promoter regions and six epigenetic modifications in enhancer regions. Further analysis of the effects in different locations revealed that the epigenetic regulation of CTCF binding was location-specific and cancer cell line-specific. Moreover, H3K4me2 and H3K9ac showed the potential association with immune regulation of disease. Taken together, our method can contribute to improve the understanding of the epigenetic regulation of CTCF binding and provide potential therapeutic targets for treating tumors associated with CTCF.

Funder

National Natural Science Foundation of China

Harbin Medical University

The Department of Heilongjiang Province

Heilongjiang Natural Science Fund

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

Reference61 articles.

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