Early in 2011, Chestnut and coworkers investigated the global 5-mC content and DNMT protein levels in nuclei and mitochondria from both brain and spinal cord motor neurons of mice, as well as in cortical motor neurons from 12 patients with amyotrophic lateral sclerosis (ALS), revealing that motor neurons engage epigenetic mechanisms to drive apoptosis, involving up-regulation of DNMTs and increased global DNA methylation in both nuclei and mitochondria (22). Here, DNMT1 is linked to amyotrophic lateral sclerosis.