Epigenetic regulation, the molecular basis of transcriptional regulation, is the most import layer for spatial-temporally controlling global and local gene levels and patterns. In previous studies, the functions of epigentic modifications are mainly interrogated byperturbations of epigenetic modifiers or correlation analysis of genetranscription and modification enrichment. However, one epigenetic modifieralways has several downstream targets and one specific site can be modified byseveral modifiers. Actually, the specific role of site-specific modifications, such ashistone modifications and DNA modifications, remains largely unclear in early developmental processes and cell fate determination, at least,without causal evidences.
Along with fascinating development of CRISPR/Cas9-based genomeediting toolkits, including epigenome editors, base editors, and prime editors,we can achieve complicated engineering of genome and epigenome in culturedcells and animal models, with some extended limitations under some circumstances. Thus, we have the following research interests:
i. We try to establish transcriptomic and epigenomic landscape during mouse preimplantation and postimplantation embryonic development, regarding mRNA splicing, DNA methylation, and histone modifications. We also explore the regulatory relationship between different modifications and chromatin structures.
ii. We engineer genome editing tools to improve their on-editing efficiencies and decrease their DNA and RNA off-targerting abilities. We also develop novel genome editing tools to expand their applications.
iii. We apply editing tools to generate disease models, to investigate the causal relatioship between developmental processes and epigenetic modifications, and to elucidate roles of site-specific modifications by epigenome engineering.
Publications:
1. Qiao, Y.*,#, Ren, C.*, Huang, S.*,Yuan, J.*, Liu, X.*, Fan, J., Lin, J., Wu, S., Chen, Q., Bo, X., Li, X., Huang,X., Liu, Z.#, Shu, W.#. High-resolution annotation of the mouse preimplantationembryo transcriptome using long-read sequencing. Nature Comm.11, Article number: 2653 (2020)
2. Qiao, Y. *,#,Wang, Z. *, Tan, F. *, Chen, J*., Lin, J., Yang, J., Li, H., Wang, X., Sali,A., Zhang, L#. and Zhong, G#. (2020) Enhancer Reprogramming within Pre-existingTopologically Associated Domains Promotes TGF-beta-Induced EMT and CancerMetastasis. Mol Ther. 1;S1525-0016(20)30290-2 (2020).doi: 10.1016/j.ymthe.2020.05.026.
3. Yang, G.*, Zhou, C,*,Wang, R.,*, Huang, S, Wei, Y., Yang, X., Liu, Y., Li, J., Lu, Z., Ying, W., Li,X., Jing, N., Huang, X.#, Yang, H.#, Qiao, Y.# (2019) Baseediting-mediated R17H substitution in histone H3 reveals itsmethylation-dependent regulation of Yap signaling and early mouse embryodevelopment. Cell Rep 26(2), 302-312
4. Liu, Y.*, Li, J.*,Zhou, C.* Meng, B.*, Wei, Y., Yang, G., Lu, Z., Shen, Q., Zhang, Y., Yang, H.#,Qiao, Y.#. (2019) Allele-specific genome editing of imprintinggenes by preferentially targeting non-methylated loci using Staphylococcusaureus Cas9 (SaCas9). Science Bulletin. 64 (21):1592-1600.
5. Yang, X.*, Hu, B. *,Liao, J. *, Qiao, Y.*#, Chen, Y., Qian, Y., Feng, S., Yu, F.,Dong, J., Hou, Y. , Xu, H. , Wang, R., Peng, G., Li, J. #, Tang, F. #, Jing,N.#. (2019) Distinct enhancer signatures in the mouse gastrula delineateprogressive cell fate continuum during embryo development. Cell Res29: 911–926.
6. Yang, X.*, Hu, B.*,Hou, Y.*, Qiao, Y.*#, Wang, R., Chen, Y., Qian, Y., Feng, S.,Chen, J., Liu, C., Peng, G., Tang, F.# and Jing, N#. (2018) Silencing ofdevelopmental genes by H3K27me3 and DNA methylation reflects the discrepantplasticity of embryonic and extraembryonic lineages. Cell Res28(5), 593-596.
7. Yang, X.*, Wang, R.*,Wang, X.*, Cai, G., Qian, Y., Feng, S., Tan, F., Chen, K., Tang, K., Huang, X.,Jing, N.# and Qiao, Y.# (2018) TGFbeta signalinghyperactivation-induced tumorigenicity during the derivation of neuralprogenitors from mouse ESCs. J Mol Cell Biol 10(3), 216-228.
8. Wang, X.J.*, Qiao,Y.*, Xiao, M.M.*, Wang, L., Chen, J., Lv, W., Xu, L., Li, Y., Wang, Y.,Tan, M.D., Huang, C., Li, J., Zhao, T.C., Hou, Z., Jing, N. and Chin, Y.E.(2017) Opposing Roles of Acetylation and Phosphorylation in LIFR-DependentSelf-Renewal Growth Signaling in Mouse Embryonic Stem Cells. Cell Rep18(4), 933-946.
9. Qiao, Y.*,Wang, R.*, Yang, X., Tang, K. and Jing, N. (2015) Dual roles of histone H3lysine 9 acetylation in human embryonic stem cell pluripotency and neuraldifferentiation. J Biol Chem 290(16), 9949.
10. Qiao, Y.*,Wang, X.*, Wang, R., Li, Y., Yu, F., Yang, X., Song, L., Xu, G., Chin, Y.E. andJing, N. (2015) AF9 promotes hESC neural differentiation through recruitingTET2 to neurodevelopmental gene loci for methylcytosine hydroxylation. CellDiscov 1, 15017.
11. Qiao, Y.*, Zhu, Y., Sheng, N.,Chen, J., Tao, R., Zhu, Q., Zhang, T., Qian, C. and Jing, N. (2012) AP2gammaregulates neural and epidermal development downstream of the BMP pathway atearly stages of ectodermal patterning. Cell Res 22(11),1546-1561.