Small molecules capable of activating DNA methylation–repressed genes targeted by the p38 mitogen-activated protein kinase pathway

Xiang Li, Erchang Shang, Qiang Dong, Yingfeng Li, Jing Zhang, Shaohua Xu, Zuodong Zhao, Wei Shao, Cong Lv, Yong Zheng, Hailin Wang, Xiaoguang Lei, Bing Zhu and Zhuqiang Zhang; J. Biol. Chem. 2018 293: 7423-7436. doi: 10.1074/jbc.RA117.000757

DNA methylation changes in certain loci can directly cause certain neurological diseases, including fragile X syndrome, Friedreich’s ataxia and spinal muscular atrophy, which can be caused by DNA hypermethylation on the promoter regions of the FMR1, FXN and SMN genes respectively. Thus, small molecules that can activate genes silenced by DNA methylation are of clinical relevance.