title: Cell-Wide DNA De-Methylation and Re-Methylation of Purkinje Neurons in the Developing Cerebellum.
abstract: Global DNA de-methylation is thought to occur only during pre-implantation and gametogenesis in mammals. Scalable, cell-wide de-methylation has not been demonstrated beyond totipotent stages. Here, we observed a large scale de-methylation and subsequent re-methylation (CDR) (including 5-methylcytosine (5mC) and 5-hydroxylmethylcytosine (5hmC)) in post-mitotic cerebellar Purkinje cells (PC) through the course of normal development. Through single cell immuno-identification and cell-specific quantitative methylation assays, we demonstrate that the CDR event is an intrinsically scheduled program, occurring in nearly every PC. Meanwhile, cerebellar granule cells and basket interneurons adopt their own DNA methylation program, independent of PCs. DNA de-methylation was further demonstrated at the gene level, on genes pertinent to PC development. The PC, being one of the largest neurons in the brain, may showcase an amplified epigenetic cycle which may mediate stage transformation including cell cycle arrest, vast axonal-dendritic growth, and synaptogenesis at the onset of neuronal specificity. This discovery is a key step toward better understanding the breadth and role of DNA methylation and de-methylation during neural ontology.
authors: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States of America.|Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States of America.
authors: Feng C
authors: FC
authors: Zhou
authors: Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States of America.
authors: Marisol
authors: M
authors: Resendiz
authors: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States of America.
authors: Chiao-Ling
authors: CL
authors: Lo
authors: Department of Anatomy & Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, 46202, United States of America.
authors: Yuanyuan
authors: Y
authors: Chen
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000235:genetics; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D051379:Mice; D011689:Purkinje Cells / Q000166:cytology* / Q000378:metabolism*; D059010:Single-Cell Analysis