The multiple functions of CTCF in breast cancer cells. (A) CTCF as transcriptional regulator regulates target gene expression through binding with co-factors such as ER and TP53 at unmethylated CpG regions. (B) CTCF as insulator prevents enhancer activity through regulation of ER binding to neighboring genes, TFF3 and TMPRSS3, at the TFF locus. (C) CTCF is involved in inverse expression of genes which have alternative promoters. After ER treatment, long-form transcript of NET1 was highly expressed whereas short-form transcript separated by CTCF was decreased. (D) Decreased CTCF after ER treatment induces chromatin looping to connect distal and proximal ERs at the P2RY2 locus.