MACMIC Reveals A Dual Role of CTCF in Epigenetic Regulation of Cell Identity Genes

Guangyu Wang, Bo Xia, Man Zhou, Jie Lv, Dongyu Zhao, Yanqiang Li, Yiwen Bu, Xin Wang, John P. Cooke, Qi Cao, Min Gyu Lee, Lili Zhang, Kaifu Chen

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Numerous studies of relationship between epigenomic features have focused on their strong correlation across the genome, likely because such relationship can be easily identified by many established methods for correlation analysis. However, two features with little correlation may still colocalize at many genomic sites to implement important functions. There is no bioinformatic tool for researchers to specifically identify such feature pairs. Here, we develop a method to identify feature pairs in which two features have maximal colocalization minimal correlation (MACMIC) across the genome. By MACMIC analysis of 3306 feature pairs in 16 human cell types, we reveal a dual role of CCCTC-binding factor (CTCF) in epigenetic regulation of cell identity genes. Although super-enhancers are associated with activation of target genes, only a subset of super-enhancers colocalized with CTCF regulate cell identity genes. At super-enhancers colocalized with CTCF, CTCF is required for the active marker H3K27ac in cell types requiring the activation, and also required for the repressive marker H3K27me3 in other cell types requiring repression. Our work demonstrates the biological utility of the MACMIC analysis and reveals a key role for CTCF in epigenetic regulation of cell identity. The code for MACMIC is available at

Original languageEnglish (US)
Pages (from-to)140-153
Number of pages14
JournalGenomics, Proteomics and Bioinformatics
Issue number1
StatePublished - Feb 2021


  • CCCTC-binding factor
  • Correlation
  • H3K27ac
  • H3K27me3
  • Mutual information

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Computational Mathematics


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