In recent years, increasing evidence indicates that multiple neurodevelopmental, neurodegenerative, and psychiatric disorders are caused, in part, by aberrant epigenetic modifications. We have examined the dynamic DNA modifications during neurodevelopment and aging, and their roles in the pathogenesis of human diseases.
Using the technology that we developed, we generated the first genome-wide maps of 5hmC during brain development, providing a detailed epigenomic view of regulated 5hmC in the CNS. Our analyses suggest that 5hmC-mediated epigenetic regulation may broadly impact brain development, and its dysregulation could contribute to autism.
Besides autism, our recent works have also linked 5hmC and Tet proteins to multiple neurological disorders, including fragile X-related disorders, ischemic brain injury and Alzheimer’s diseases.
Szulwach, K.E., Li, X., Li, Y., Song, C.X., Wu, H., Dai, Q., Irier, H., Upadhyay, A.K., Gearing, M., Levey, A.I., Vasanthakumar, A., Godley, L.A., Chang, Q., Cheng, X., He, C. and Jin, P. (2011) 5-hydroxymethylcytosine-mediated epigenetic dynamics during postnatal neurodevelopment and aging. Nature Neuroscience, 14: 1607-1616. PMC3292193
Yao, B., Lin, L., Street, R.C., Zalewski, Z.A., Galloway, J.N., Wu, H., Nelson, D.L., and Jin, P. (2013) Genome-wide alteration of 5-hydroxymethylcytosine in a mouse model of fragile X-associated tremor/ataxia syndrome. Human Molecular Genetics, 23: 1095-1107. PMC3900112
Yao B, Cheng Y, Wang Z, Li Y, Chen L, Huang L, Zhang W, Chen D, Wu H, Tang B and Jin P. (2017) DNA N6-methyladenine is dynamically regulated in the mouse brain following environmental stress. Nature Communications, 8: 1122. PMC5654764
Yao B, Li, Y., Wang Z, Chen L, Poidevin M, Zhang C, Lin L, Wang F, Bao H, Jiao B, Lim J, Cheng Y, Huang L, Philips BL, Xu T, Duan R, Moberg KH, Wu H, Jin P (2018) Active N6-Methyladenine demethylation by DMAD regulates gene expression by coordinating with Polycomb protein in neurons. Molecular Cell, 71: 848-857. PMC6136845