Peng Jin, Ph.D.
Department of Human Genetics
Lab: Whitehead 335 & 355
Additional Contact Information
Whitehead Biomedical Research Building
615 Michael St.
Atlanta, GA 30322
Dr. Peng Jin received his doctorate degree in Molecular and Developmental Biology from Cincinnati Children’s Hospital/University of Cincinnati, and postdoctoral training at Emory University. At Emory, Dr. Jin is interested in the roles of noncoding RNAs and epigenetic modulation in neural development and brain disorders. Dr. Jin is the recipient of Beckman Young Investigator Award, Basil O'Connor Scholar Research Award, Alfred P. Sloan Research Fellow in Neuroscience, and NARSAD Independent Investigator Award.
Our research philosophy combines various disciplines (biochemistry, genetics, chemistry, human genetics/genomics, and bioinformatics) to understand the functions and mechanisms of epigenetics and noncoding RNAs in neurodevelopmental and neurodegenerative disorders.
Epigenetic alphabet in Neurodevelopment and Aging
Cytosine methylation serves as a critical epigenetic mark by modifying DNA-protein interactions that influence transcriptional states, and ultimately cellular identity. 5mC has generally been viewed as a stable and long-lasting covalent modification to DNA; however, the fact that 5mC can be enzymatically modified to 5hmC by Tet family proteins through Fe(II) a-KG-dependent hydroxylation gives a new perspective on the previously observed plasticity in 5mC-dependent regulatory processes. In addition, 5hmC can be further oxidized to 5fC and 5caC by TET proteins, and 5fC and 5caC can be removed by DNA glycosylase TDG, implicating 5mC oxidation in active DNA demethylation. Together, these studies provide an emerging paradigm in which 5mC oxidation plays important roles in sculpting a cell’s epigenetic landscape and developmental potential through the regulation of dynamic DNA methylation states. Currently we are focusing on understanding their roles in gene regulation/neural development as well as contributions to neurological disorders.
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder that results from the intermediate expansion (55-200 repeats) of trinucleotide CGG repeats in the 5’ UTR of the FMR1 gene. FXTAS is one of the most common inheritable neurodegenerative disorders in males. Our earlier work has demonstrated that overproduced riboCGG (rCGG) repeats in the 5’ UTR of FMR1 mRNA are toxic, which provided the first example of RNA itself being sufficient to cause neurodegeneration. Over the last ten years, we have been continuing to study the molecular mechanisms of RNA-mediated neurodegeneration and develop potential therapeutics using both fly and mouse models. More recently we have also developed a fly model demonstrating the toxicity of the RNA produced from an expanded GGGGCC (G4C2) repeat in C9ORF72 gene, which has been shown an important cause of both ALS and FTD. These works provide a framework for the emerging field of RNA-mediated neurodegeneration.
Modulation of Small RNA Pathways
Small noncoding RNA guides, including microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), and endogenous small interfering RNAs (esiRNAs), are 18 to 30 nucleotides in length and can shape diverse cellular pathways. Understanding the mechanism of the small RNA pathway is of great importance. Despite the identification of the major siRNA/miRNA pathway components over the last decade, much more remains to be uncovered about the regulation of the RNAi pathway itself. Using chemical and genetic approaches, we are interested in how the small RNA pathway is regulated in general.
Areas of Specialization
- Epigenetic regulation in brain development
- Non-coding RNAs in neural development and brain disorders
- PhD, Molecular and Developmental Biology, University of Cincinnati College of Medicine and Cincinnati Children's Hospital Research Foundation, Ohio,1999
- BS, Molecular Biology, University of Science and Technology of China, P.R. China,1994
- View publications on PudMed
Huang, H., Li, Y., Szulwach, K.E., Zhang, G., Jin, P.*, and Chen, D.* (2014) AGO3 Slicer Activity Regulates Mitochondria-Nuage Localization of Armitage and piRNA Amplification. Journal of Cell Biology, 206, 217-230. (*: Co-Corresponding authors)
Yao, B. and Jin, P. (2014) Unlocking epigenetic codes in neurogenesis. Genes & Development, 28:1253-1271.
Zhu, G., Li, Y., Zhu, F., Wang, T., Jin, W., Mu, W., Lin, W., Tan, W., Li, W., Street, R.C., Peng, S., Zhagn, J., Feng, Y., Warren, S.T., Sun, Q., Jin, P.*, and Chen, D.* (2014) Coordination of engineered factors with TET1/2 promotes early stage epigenetic modification during somatic cell reprogramming. Stem Cell Reports, 2: 253-261 (*: Co-Corresponding authors).
Wang, T., Wu, H., Li, Y., Szulwach, K.E., Lin, L., Li, X., Chen, I.P., Goldlust, I.S., Chamberlain, S.J., Ananiev, G., Mowrey, J., Han, J.W., Yoon, Y., Rudd, M.K., Song, C.X., He, C., Chang, Q., Warren, S.T., and Jin, P. (2013) Subtelomeric hotspots of aberrant 5-hydroxymethylcytosine-mediated epigenetic modifications during reprogramming to pluripotency. Nature Cell Biology, 15: 700-711.
Song, C.X., Szulwach, K.E., Dai, Q., Fu, Y., Mao, S.Q., Lin, L., Street, C., Li, Y., Poidevin, M., Wu, H., Gao, J., Liu, P., Li, L., Xu, G.L.,Jin, P.*, and He, C.* Genome-wide Profiling of 5-Formylcytosine reveals its roles in epigenetic priming. Cell, 153: 678-691. (*: Co-Corresponding authors).
Xu, Z., Poidevin, M., Li, X., Li, Y., Shu, L., Nelson, D.L., Li, H., Gearing, M., Wingo, T.S., and Jin, P. (2013) Expanded Hexanucleotide GGGGCC Repeat RNA Associated with ALS/FTD Causes Neurodegeneration. Proceedings of the National Academy of Sciences, 110: 7778-7783.
Li, Y., Lin, L., Li, Z., Ye, X., Xiong, K., Aryal, B., Xu, Z., Paroo, Z., Liu, Q., He, C., and Jin, P. (2012) Iron Homeostasis Regulates the Activity of the MicroRNA Pathway through Poly(C)-Binding Protein 2. Cell Metabolism, 15, 895-904.
Yu, M., Hon, G.C., Szulwach, K.E., Song, C.X., Zhang, L., Kim, A., Li, X., Dai, Q., Shen, Y., Park, B., Min, J.H., Jin, P. *, Ren, B. *, and He. C. * (2012) Base-Resolution Analysis of 5-Hydroxymethylcytosine in the Mammalian Genome. Cell, 149, 1368-1380 (*: Co-Corresponding authors).
Tan H., Poidevin, M., He, L., Chen, D., and Jin, P. (2012) MicroRNA-277 Modulates the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats. PLoS Genetics, e1002681.
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 neurodevelopment and aging. Nature Neuroscience, 14: 1607-1616.
Szulwach, K.E., Li, X., Li, Y., Song, C.X., Han, J.W., Kim, S., Namburi, S., Hermetz, K., Kim, J.J., Rudd, M.K., Yoon, Y., Ren, B., He, C. and Jin, P. (2011) Integrating 5-hydroxymethylcytosine into the Epigenomic Landscape of Human Embryonic Stem Cells. PLoS Genetics, 7(6): e1002154. 59.
Guo, W., Zhang, L., Christopher, D.M., Teng, Z.Q., Fausett, S.R., Liu, C., George, O.L., Klingensmith, J., Jin, P. and Zhao, X. (2011) RNA-Binding Protein FXR2 Regulates Adult Hippocampal Neurogenesis by Reducing Noggin Expression. Neuron, 70: 924-938.
Qurashi, A., Li, W., Zhou, J.Y., Peng, J., and Jin, P. (2011) Nuclear Accumulation of Stress Response mRNAs Contributes to the Neurodegeneration Caused by Fragile X Premutation rCGG Repeats. PLoS Genetics, 7(6): e1002102.
Guo, W., Allan, A.M., Zong, R., Zhang, L., Johnson, E.B., Schaller, E.G., Murthy, A.C., Goggin, S.L., Eisch, A.J., Ooostra, B.A., Nelson, D.L., Jin, P. and Zhao, X. (2011) Ablation of Fmrp in adult neural stem cells disrupts hippocampus-dependent learning. Nature Medicine, 17(5): 559-65.
Song, C.X., Szulwach, K.E., Fu, Y., Dai, Q., Yi, C., Li, X., Li, Y., Chen, C.H., Zhang, W., Jian, X., Wang, J., Zhang, L., Looney, T.J., Zhang, B., Godley, L.A., Hicks, L.M., Lahn, B.T., Jin, P.*, and He, C*. (2010) A Selective chemical labeling reveals the genome-wide distribution of 5-hydroxymethylcytosine. Nature Biotechnology, 29(1): 68-72. (*: Co-Corresponding authors).
Li, Y., He, C. and Jin, P. (2010). Emergence of Chemical Biology Approaches to the RNAi/miRNA Pathway. Chemistry & Biology, 17(6): 584-589.
Liu, C., Teng, Z. Q., Satistevan, N.J., Szulwach, K. E., Guo, W., Jin, P., and Zhao, X. (2010) Epigenetic regulation of miR-184 by MBD1 governs neural stem cell proliferation and differentiation. Cell Stem Cell, 6, 433-444.
Luo, Y., Shan, G., Smrt, R.D., Li, X., Duan, R., Barkho, B.Z., Li, W., Jin, P.*, and Zhao, X.* (2010) Fragile X mental retardation protein regulates adult neurogenesis. PLoS Genetics, 6(4): e1000898. (*: Co-Corresponding authors).
Szulwach K. E., Li, X., Smrt, R.D., Li, Y., Luo, Y., Lin, L., Satistevan, N.J., Li, W. Zhao, X., and Jin, P. (2010) MeCP2-mediated crosstalk between microRNA and epigenetic regulation in adult neurogenesis. Journal of Cell Biology, 189, 127-141.
Li, X. and Jin, P. (2010). Roles of small regulatory RNAs in the determination of neuronal identity. Nature Reviews Neuroscience, 11(5): 329-338.
Yang, Y., Xu, S., Xia, L., Wang, J., Jin, P.* and Chen, D.* (2009) MicroRNA Bantam is associated with Drosophila Fragile X mental retardation protein and regulates the fate of germline stem cells. PLoS Genetics, 5(4): e1000444. (*: Co-Corresponding authors)
Shan, G.*, Li, Y.* (*Equal Contribution), Zhang, J., Li, W., Szulwach, K., Duan, R., Faghihi, M.A., Khalil, A., Lu, L., Paroo, Z., Chan, A.W.S., Shi, Z., Liu, Q., Wahlestedt, C., He, C., and Jin, P. (2008). A small molecule enhances RNA interference and promotes microRNA processing. Nature Biotechnology, 8, 933-940.
Chang, S., Bray, S.M., Li, Z., Zarnescu, D.C., He, C., Jin, P.,and Warren, S.T. (2008). Identification of small molecules rescuing morphological, biochemical and behavioral phenotypes of fragile X syndrome in Drosophila. Nature Chemical Biology, 4, 256-263.
Alisch, R.S., Jin, P., Epstein, M., Caspary, T., and Warren, S.T. (2007). Argonaute2 is Essential for Mammalian Gastrulation and Proper Mesoderm Formation. PLoS Genetics, 3, 2565-2571.
Sofola, O.A.*, Jin, P.* (equal contribution), Qin, Y., Duan, R., Liu, H., de Haro, M., Nelson, D.L., and Botas, J. (2007). RNA binding proteins hnRNP A2/B1 and CUGBP1 suppress Fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. Neuron, 16, 565-571.
Jin, P.*, Duan, R., Qurashi, A., Qin, Y., Tian, D., Rosser, T.C., Liu, H., Feng, Y., and Warren, S.T.* (2007). Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of Fragile X Tremor/Ataxia Syndrome. Neuron, 16, 556-564. (*: Co-Corresponding authors)