TY - JOUR TI - Methylated cis-regulatory elements mediate KLF4-dependent gene transactivation and cell migration AU - Wan, Jun AU - Su, Yijing AU - Song, Qifeng AU - Tung, Brian AU - Oyinlade, Olutobi AU - Liu, Sheng AU - Ying, Mingyao AU - Ming, Guo-li AU - Song, Hongjun AU - Qian, Jiang AU - Zhu, Heng AU - Xia, Shuli A2 - Ren, Bing VL - 6 PY - 2017 DA - 2017/05/29 SP - e20068 C1 - eLife 2017;6:e20068 DO - 10.7554/eLife.20068 UR - https://doi.org/10.7554/eLife.20068 AB - Altered DNA methylation status is associated with human diseases and cancer; however, the underlying molecular mechanisms remain elusive. We previously identified many human transcription factors, including Krüppel-like factor 4 (KLF4), as sequence-specific DNA methylation readers that preferentially recognize methylated CpG (mCpG), here we report the biological function of mCpG-dependent gene regulation by KLF4 in glioblastoma cells. We show that KLF4 promotes cell adhesion, migration, and morphological changes, all of which are abolished by R458A mutation. Surprisingly, 116 genes are directly activated via mCpG-dependent KLF4 binding activity. In-depth mechanistic studies reveal that recruitment of KLF4 to the methylated cis-regulatory elements of these genes result in chromatin remodeling and transcription activation. Our study demonstrates a new paradigm of DNA methylation-mediated gene activation and chromatin remodeling, and provides a general framework to dissect the biological functions of DNA methylation readers and effectors. KW - DNA methylation KW - histone modification KW - cell migration KW - KLF4 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -