
Dynamic DNA methylation regulates neuronal flexibility
Description
Epigenetic modifications of chromatin, including the genomic DNA and histone proteins, play critical roles in orchestrating transcriptomes of all cell types. We found that neuronal stimulation induces region-specific active DNA demethylation in a Gadd45b- and TET1-dependent fashion in the adult mouse dentate granule neurons in vivo (Ma et al. Science 2009; Guo et al. Cell 2011). Our genome-wide analysis further revealed that 1.4% of all CpGs measured exhibit rapid activity-induced demethylation or de novo methylation (Guo et al. Nat. Neurosci. 2011). These activity-modified CpGs exhibit a broad genomic distribution with significant enrichment in low-CpG density regions, and are associated with brain-specific genes related to neuronal plasticity. Our single-base methylome analysis discovered significant levels of nonCpG methylation in these neurons and we identified DNMT3A and MeCP2 as a writer and a reader for nonCpG DNA modification (Guo et al. Nat. Neurosci. 2013). More recently, our studies suggest that active DNA demethylation and DNA repair serve as a synaptic activity sensor to epigenetically regulate fundamental properties and meta-plasticity of neurons and animal behavior (Yu et al. Nat. Neurosci. 2015). Together, our studies implicate novel modifications of the neuronal DNA methylome as a previously under-appreciated mechanism for activity-dependent epigenetic regulation in the adult nervous system under both physiological and pathological conditions.
Speaker Bio
Hongjun Song, Ph.D. is a Professor in the Department of Neurology and The Solomon Snyder Department of Neuroscience and Director of the Stem Cell Biology Program at Institute for Cell Engineering of Johns Hopkins University School of Medicine. He received his. B.S from Peking University, M.A. from Columbia University and Ph.D. from University of California at San Diego. The research in Dr. Song’s laboratory focuses on plasticity in the adult mammalian nervous system, in particularly, adult neurogenesis and neuroepigenetics. His laboratory also uses patient-derived stem cells to model brain development and neurological disorders. He was listed as a Thomson Reuter Highly Cited Researcher in 2014. He serves on a number of editorial boards and is currently Editor-in-Chief of Frontiers in Biology. Dr. Song has won several awards Young Investigator Award from the Society for Neuroscience, and Jacob Javits Neuroscience Investigator Award from National Institute of Health.