Perelman School of Medicine at the University of Pennsylvania

Song Lab

Neurons in the hippocampus

Neuroepigenetics & Neuroepitranscriptomics

Neuroepigenetics & Neuroepitranscriptomics

Contrary to the long-held dogma that DNA methylation is a stable epigenetic mark in post-mitotic neurons, it is now recognized to be a robust form of plasticity in the adult nervous system. We have made significant contributions to the current understanding of epigenetic DNA modifications in the nervous system. The laboratory has delineated molecular mechanisms mediating active DNA demethylation in mature neurons in vivo. More recently, we showed that the neuronal DNA demethylation pathway plays fundamental roles in neuronal function, including regulation of basal levels of synaptic transmission and homeostatic synaptic plasticity. We have established a pipeline for high-throughput sequencing analyses, including RNA-seq, Chip-seq, Bisulfite-seq, ATAC-seq, and single-cell RNA-seq, and designed custom software programs for bioinformatic analyses. Currently, we are developing novel technologies to reveal epigenetic landscapes during neurogenesis and address potential functions of different epigenetic mechanisms in regulating distinct neurogenesis processes and neuronal functions.

Recent high-throughput sequencing approaches have also revealed a dynamic “epitranscriptome” landscape for many mRNA modifications in various organisms, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 5-hydroxymethylcytosine (hm5C), pseudouridine (y), and 2’-O-methylnucleotides. Currently, we are addressing the functions and mechanisms of various RNA modifications in the developing and mature mammalian nervous system.


Selected Publications

Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation

Cell

Yoon KJ, Rojas Ringeling F, Vissers C, Jacob F, Pokrass M, Jimenez-Cyrus D, Su Y, Kim NS, Zhu Y, Zheng L, Kim S, Wang X, Dore L, Jin P, Regot S, Zhuang X, Canzar S, He C, Ming GL, Song H. Temporal Control of Mammalian Cortical Neurogenesis by m6A Methylation. Cell. 2017 Sep 28.

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Neuronal activity modifies the chromatin accessibility landscape in the adult brain

Nature Neuroscience

Su Y, Shin J, Zhong C, Wang S, Roychowdhury P, Lim J, Kim D, Ming GL, Song H. Neuronal activity modifies the chromatin accessibility landscape in the adult brain. Nat Neurosci. 2017 Mar;20(3):476-483. PMC5325677.

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Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair

Nature Neuroscience

Yu, H., Su, Y., Shin, J., Zhong, C., Guo, J.U., Weng, Y-l., Gao, F., Geschwind, D.H., Coppola, G., Ming, G-l., and Song, H. (2015). Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair. Nature Neuroscience 18, 836-843.

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Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain

Nature Neuroscience

Guo, J.U., Su, Y., Shin, J.H., Shin, J., Li, H., Xie, B., Zhong, C., Hu, S., Le, T., Fan, G., Zhu, H., Chang, Q., Gao, Y., Ming, G.L., Song, H. (2014). Distribution, recognition and regulation of non-CpG methylation in the adult mammalian brain. Nature Neuroscience 17, 215-22.

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Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain

Cell

Guo, J.U., Su, Y., Zhong, C., Ming, G.L., and Song, H. (2011). Hydroxylation of 5-methylcytosine by TET1 promotes active DNA demethylation in the adult brain. Cell 145, 423-34.

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Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis

Science

Ma, D.K., Jang, M.H., Guo, J.U., Kitabatake, Y., Chang, M.L., Pow-Anpongkul, N., Flavell, R.A., Lu, B., Ming, G.L., and Song, H-j. (2009). Neuronal activity-induced Gadd45b promotes epigenetic DNA demethylation and adult neurogenesis. Science 323, 1074-7.

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