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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.<\/jats:p>","DOI":"10.1093\/bib\/bbaa004","type":"journal-article","created":{"date-parts":[[2020,1,9]],"date-time":"2020-01-09T12:20:39Z","timestamp":1578572439000},"page":"589-600","source":"Crossref","is-referenced-by-count":5,"title":["Systematical identification of cell-specificity of CTCF-gene binding based on epigenetic modifications"],"prefix":"10.1093","volume":"22","author":[{"given":"Jie","family":"Wu","sequence":"first","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qian","family":"Song","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weida","family":"Wang","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Xia","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaowen","family":"Chen","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yun","family":"Xiao","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaohan","family":"Xu","sequence":"additional","affiliation":[{"name":"Bioinformatics at Harbin Medical University, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"issue":"12","key":"2021012203203522600_ref1","doi-asserted-by":"crossref","first-page":"7612","DOI":"10.1128\/MCB.13.12.7612","article-title":"CTCF, a conserved nuclear factor required for optimal transcriptional activity of the chicken c-myc gene, is an 11-Zn-finger protein differentially expressed in multiple forms","volume":"13","author":"Klenova","year":"1993","journal-title":"Mol Cell Biol"},{"issue":"12","key":"2021012203203522600_ref2","first-page":"1743","article-title":"A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5\u2032-flanking sequence of the chicken c-myc gene","volume":"5","author":"Lobanenkov","year":"1990","journal-title":"Oncogene"},{"issue":"3","key":"2021012203203522600_ref3","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/S0092-8674(00)81967-4","article-title":"The protein CTCF is required for the enhancer blocking activity of vertebrate insulators","volume":"98","author":"Bell","year":"1999","journal-title":"Cell"},{"issue":"17","key":"2021012203203522600_ref4","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1101\/gad.399506","article-title":"CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus","volume":"20","author":"Splinter","year":"2006","journal-title":"Genes Dev"},{"issue":"3","key":"2021012203203522600_ref5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/0092-8674(90)90532-J","article-title":"Modular structure of a chicken lysozyme silencer: involvement of an unusual thyroid hormone receptor binding site","volume":"61","author":"Baniahmad","year":"1990","journal-title":"Cell"},{"issue":"7","key":"2021012203203522600_ref6","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2009.06.001","article-title":"CTCF: master weaver of the genome","volume":"137","author":"Phillips","year":"2009","journal-title":"Cell"},{"issue":"52","key":"2021012203203522600_ref7","doi-asserted-by":"crossref","first-page":"33353","DOI":"10.1074\/jbc.272.52.33353","article-title":"The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. 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