In this study, we asked what is the status of primary epigenetic marks during the quiescent stage of the neural stem cells? Will the DNA methylation and histone methylation & acetylation, which mediate chromatin modification, modify at the cellular level preceding or during activation from the quiescent to the differentiation stage? To this end, we utilized previously established dorsal root ganglia (DRG) NSCs (22), which were cultured in a quiescent state as neurospheres in maintenance medium and can be forward to enriched medium for close observation of differentiation. We have previously characterized their differentiation profile and phenotypes in the differentiating population (22), which allowed us to evaluate the epigenetic modification at the single cell basis with a known differentiation status. Both key epigenetic marks, histone code and DNA methylation, were studied: the dimethyl-Histone H3-lysine 4 (2me-H3K4) (20) and acetylated Histone H4 (Ac-H4), associated with transcriptionally active euchromatin (10), and 3me-H3K27, associated with transcriptional repression (5,10,11), were highlighted in this study. The DNA methylation site- 5-methyl cytosine (5-MeC), DNA methylation binding protein (MBD1), and DNA methyltransferase (DNMT) 1 and 3 mediating
