个体发育和细胞分化过程决定于基因的差异表达。基因的表达与否决定于染色质结构。基因转录表达和沉默就是染色质的重塑过程。组蛋白甲基化、乙酰化、磷酸化和DNA甲基化等表观遗传修饰协同作用，调控染色质重塑过程。调控个体发育的基因同时受到多种组蛋白表观遗传修饰调控，那么决定基因转录和个体发育的组蛋白密码（histone code）是什么目前还不够清楚。我们主要利用模式动物小鼠，研究调控肺形态建成和细胞命运决定的“组蛋白密码”组成、分子识别和信号传导机理。
真核细胞的高尔基体（Golgi Apparatus）是分泌途径最重要的细胞器，其结构和功能影响细胞内蛋白质等物质的翻译后修饰、折叠和运输。但是高尔基体结构功能缺陷对个体发育和疾病发生的作用目前还不清楚。本课题组的研究重点一是揭示蛋白质甲基化修饰对细胞分泌途径细胞器，特别是高尔基体结构和功能的调控作用。我们利用蛋白质组学方法，研究蛋白质甲基转移酶与高尔基体基质蛋白等蛋白质复合体之间的相互作用，以阐明蛋白质甲基化修饰的作用机理。同时，我们通过建立小鼠Knockout模型，阐明高尔基体结构和功能在调控动物个体发育和疾病发生中的作用。
造血干细胞（HSC）向淋巴细胞分化过程决定于V（D）J重组和基因的准确转录。这些过程受组蛋白修饰等表观遗传因素的调控。淋巴细胞分化过程不正常就会导致许多疾病的发生，严重的会发生白血病。在儿童时期主要发生淋巴细胞白血病。我们主要研究组蛋白精氨酸甲基化修饰在造血干细胞向淋巴细胞分化中的作用机制。我们与北京儿童医院合作，研究蛋白质甲基化修饰与儿童白血病发生之间的对应关系。通过建立小鼠转基因和Knockout模型，揭示组蛋白精氨酸甲基化等表观遗传修饰调控淋巴细胞分化和儿童白血病发生的作用机理。
王昕（博士，NIH博士后，UCLA博士后），周忠卫（硕士，德国Leibniz Institute-Jena大学博士研究生，中山大学深圳医学院副教授），张娅（博士，NIH博士后，美国哥伦比亚大学Associate Scientist），高勤雨（实验室管理员，河北省石家庄医药公司经理），刘长国（博士，浙江农林大学教授），文雅（博士，Baylor Medical school博士后）, 张书沛（硕士，美国UC-Davis，安徽农业大学）， 卫沛（学士，上海），张瑞东（博士，北京儿童医院副主任），郜慧芳（硕士，北京儿童医院），贾慧（硕士，成都市人民医院），孙力涛（硕士，中科院生物物理所博士，美国Scripps Institute 博士后，中山大学深圳医学院教授），朱琳（硕士，首都医科大学北京儿童医院），张寒（博士，美国得克萨斯医学院博士后，医科院云南昆明医学生物研究所），刘潇（博士，首都医科大学北京儿童医院），许丽婷（博士，首都医科大学北京儿童医院，浙江大学），李静（博士，首都医科大学北京儿童医院），陈继林（博士后，中国农科院）
近年发表的论文:（*为通信作者）
2. Pang Q, Liu C, Qiao Y, Zhao J, Lam SM, Mei M, Shui G, Bao S*, Li Q*. (2021) GM130 regulates pulmonary surfactant protein secretion in alveolar type II cells. Sci China Life Sci. doi: 10.1007/s11427-020-1875-x.
3. Lam S, Zhang C, Wang Z, Ni Z, Zhang S, Yang S, Huang X, Mo L, Li J, Lee B, Mei M, Huang L, Shi M, Xu Z, Meng F, Cao W, Zhou M, Shi L, Chua G, Li B, Cao J, Wang J, Bao S, Wang Y, Song J？, Zhang？ F, Wang F, Shui G. (2021) A multi-omics investigation of the composition and function of extracellular vesicles along the temporal trajectory of COVID-19. Nature Metabolism 3:909-922.
4. Chen M, Dong F, Chen M, Shen Z, Wu H, Cen C, Cui X, Bao S, Gao F. (2021) PRMT5 regulates ovarian follicle development by facilitating Wt1 translation. Elife 10:e68930. doi: 10.7554/eLife.68930. Online ahead of print.
5. Li F, Dong C, Yang T, Bao S, Fang W, Lucas W, Zhang Z. (2021) The tea plant CsLHT1 and CsLHT6 transporters take up amino acids, as a nitrogen source, from the soil of organic tea plantations. Horticulture Research 8:
6. Yang T, Xie Y, Lu X, Yan X, Wang Y, Ma J, Cheng X, Lin S, Bao S, Wan X, Lucas W, Zhang Z. (2021) Shading Promoted Theanine Biosynthesis in the Roots and Allocation in the Shoots of the Tea Plant (Camellia sinensis L.) Cultivar Shuchazao. J. Agric. Food Chem. 69(16): 4795–4803.
7. Chen M, Wang Y, Lin L, Dong F, Wu H, Bao S, Gao F. (2020) PRMT7 is involved in regulation of germ cell proliferation during embryonic stage. Biochem Biophys Res Commun. 533(4):938-944.
8. Dong C, Li F, Yang T, Feng L, Zhang S, Li F, Li W, Xu G, Bao S, Wan X, Lucas WJ, Zhang Z. (2020) Theanine transporters identified in tea plants (Camellia sinensis L.). Plant J. 101(1):57-70.2019.
9. Li F, Li H, Dong C, Yang T, Zhang S, Bao S, Wan X, Zhang Z. (2020) Theanine transporters are involved in nitrogen deficiency response in tea plant (Camellia sinensis L.). Plant Signal Behav. 15(3):1728109.
10. Jin H, Du Z, Zhang Y, Antal J, Xia Z, Wang Y, Gao Y, Zhao X, Han X, Cheng Y, Shen Q, Zhang K, Elder RE, Benko Z, Fenyvuesvolgyi C, Li G, Rebello D, Li J, Bao S, Zhao RY, Wang D. (2020) A distinct class of plant and animal viral proteins that disrupt mitosis by directly interrupting the mitotic entry switch Wee1-Cdc25-Cdk1. Sci Adv. 6(20):eaba3418.
11. Mei M, Zhang R, Zhou Z, Ying Z, Wang J, Zhang H, Zheng H*, Bao S*. (2019) PRMT5-mediated H4R3sme2 Confers Cell Differentiation in Pediatric B-cell Precursor Acute Lymphoblastic Leukemia. Clin. Cancer Res. 25(8): 2633-2643.
12. Ding X, Jiang X, Tian R, Zhao P, Li L, Wang X, Chen S, Zhu Y, Mei M, Bao S, Liu W, Tang Z, Sun Q. (2019) RAB2 regulates the formation of autophagosome and autolysosome in mammalian cells. Autophagy. 15(10):1774-1786.
13. Li Q*, Jiao J, Li H Wan H, Zheng C, Cai J, Bao S*. (2018) Histone arginine methylation by Prmt5 is required for lung branching morphogenesis through repression of BMP signaling. J Cell Sci. 131(14): jcs217406.（Cover story）
14. Xu L, Zhang H, Mei M, Du C, Huang X, Li J, Wang Y, Bao S*, Zheng H*. (2018) Phosphorylation of serine/arginine-rich splicing factor 1 at tyrosine 19 promotes cell proliferation in pediatric acute lymphoblastic leukemia. Cancer Sci. 109(12):3805-3815.
15. Jiang Q, Lu X, Huang P, Gao C, Zhao X, Xing T, Li G, Bao S, Zheng H. (2018) Expression of miR-652-3p and Effect on Apoptosis and Drug Sensitivity in Pediatric Acute Lymphoblastic Leukemia. Biomed Res Int. 2018:5724686.
16. Hu J, Yang H, Mu J, Lu T, Peng J, Deng X, Kong Z, Bao S, Cao X, Zuo J. (2017) Nitric Oxide Regulates Protein Methylation during Stress Responses in Plants. Molecular Cell 67:1-9.
17. Liu C, Mei M, Li Q, Roboti P, Pang Q, Ying Z, Gao F, Lowe M*, Bao S*. (2017) Loss of the golgin GM130 causes Golgi disruption, Purkinje neuron loss, and ataxia in mice. Proc Natl Acad Sci U S A. 114(2):346-351.（Cover story）
18. Han F, Liu C, Zhang L, Chen M, Zhou Y, Qin Y, Wang Y, Chen M, Duo S, Cui X, Bao S, Gao F*. (2017) Globozoospermia and lack of acrosome formation in GM130-deficient mice. Cell Death & Disease 8: e2532
19. Li Q, Zhao Y, Yue M, Xue Y,
Bao S*.（2016）The Protein Arginine Methylase 5 (PRMT5/SKB1) Gene Is Required for the Maintenance of Root Stem Cells in Response to DNA Damage.
J Genet Genomics 43(4):187-97.（Cover story）
20. Ying Z, Mei M, Zhang P, Liu C, He H, Gao F, Bao S*. (2015) Histone Arginine Methylation by PRMT7 Controls Germinal Center Formation via Regulating Bcl6 Transcription. The Journal of Immunology 195(4):1538-1547.
21. Zhang H, Cheng H, Wang Q, Zeng X, Chen Y, Yan J, Sun Y, Zhao X, Li W, Gao C, Gong W, Li B, Zhang R, Nan L, Wu Y, Bao S*, Han J,* & Zheng H*. (2015) An advanced fragment analysisbased individualized subtype classification of pediatric acute lymphoblastic leukemia. Sci Rep. 5:12435
22. Wang Y, Zhu T, Li Q, Liu C, Han F, Chen M, Zhang L, Cui X, Qin Y, Bao S*, Gao F*. (2015) Prmt5 is required for germ cell survival during spermatogenesis in mice. Sci Rep. 5:11031
24. Li Q, Li Y, Gu B, Fang L, Zhou P, Bao S, Huang L, Dai X. (2015) Akt Phosphorylates Wnt Coactivator and Chromatin Effector Pygo2 at Serine 48 to Antagonize Its Ubiquitin/Proteasome-mediated Degradation. J Biol Chem. 290(35):21553-67.
25. Zhang H, Zhu L, He H, Zhu S, Zhang W, Liu X, Zhao X, Gao C, Mei M,
Bao S*, Zheng H*. (2014) NF-kappa B mediated Up-regulation of CCCTC-binding factor in pediatric acute lymphoblastic leukemia.
Molecular Cancer 13(5).
26. Fan H, Zhang Z, Wang N, Cui Y, Sun H, Liu Y, Wu H, Zheng S, Bao S*, Ling H* (2014) SKB1/PRMT5-mediated histone H4R3 dimethylation of Ib subgroup bHLH genes negatively regulates iron homeostasis in arabidopsis thaliana. Plant Journal 77(2):209-221.
27. Yue M, Li Q,
Zhang Y,
Zhao Y, Zhang Z,
Bao S*. (2013) Histone H4R3 methylation catalyzed by SKB1/PRMT5 is required for maintaining shoot apical meristem .
PLoS One 8(12):.
29.
Zou L,
Zhang H,
Du C,
Liu X,
Zhu S,
Zhang W,
Li Z,
Gao C,
Zhao X,
Mei M,
Bao S,
Zheng H. (2012) Correlation of SRSF1 and PRMT1 expression with clinical status of pediatric acute lymphoblastic leukemia.
J Hematol Oncol. 27;5:42.
30. Sun, L., Wang, M., Lv, Z., Yang, N., Liu, Y., Bao, S., Gong, W., and Xu, R. (2011) Structural Insights into Protein Arginine Symmetric Dimethylation by PRMT5. PNAS 108(51): 20538-20543.
31. Zhang, Z., Zhang, S., Zhang, Y., Wang, X., Li, D., Li, Q., Yue, M., Li, Q., Zhang, Y.E., Xu, Y., Xue, Y., Chong, K., and Bao, S*. (2011). Arabidopsis Floral Initiator SKB1 Confers High Salt Tolerance by Regulating Transcription and Pre-mRNA Splicing through Altering Histone H4R3 and Small Nuclear Ribonucleoprotein LSM4 Methylation. Plant Cell 23 (1):396-411.
32. Guo S, and Bao S*. (2010) srGAP2 arginine methylation regulates cell migration and cell spreading through promoting of dimerization. J Biol Chem 285: 35133-41.
33. Jiang Y, Wang X, Bao S, Guo R, Johnson D, Shen X, Li L. (2010) The INO80 chromatin remodeling complex promotes the removal of UV lesions by the nucleotide excision repair pathway. PNAS 107(40):17274-9.
34. Zhou, Z*., Sun, X*., Zou, Z., Sun, L., Zhang, T., Guo, S., Wen, Y., Liu, L., Wang, Y., Qin, J., Li, L., Gong, W., and Bao, S*. (2010) PRMT5 regulates Golgi apparatus structure through methylation of the golgin GM130. Cell Research 20, 1023-33.
35. Ren, J., Wang, Y., Liang, Y., Zhang, Y., Bao, S. and Xu, Z. (2010). Methylation of ribosomal protein s10 by protein arginine methyltransferase 5 regulates ribosome biogenesis. J Biol Chem. 285, 12695-12705.
36. Li, Z, Zhang, W., Wu, M., Zhu, S., Gao, C., Sun, L., Zhang, R., Qiao, N., Xue, H., Hu, Y., Bao, S*, Zheng, H*. and Han, J.D*. (2009) Gene expression-based classification and regulatory networks of pediatric acute lymphoblastic leukemia. Blood, 114, 4486-4493.
37. Liu, R., Strom, A. L., Zhai, J., Gal, J., Bao, S., Gong, W., and Zhu, H. (2009). Enzymatically inactive adenylate kinase 4 interacts with mitochondrial ADP/ATP translocase. Int J Biochem Cell Biol 41, 1371-1380.
38. Sun L, Zhou Z, Xie X, and Bao S*. (2008) Study on biological activity of various truncations of human PRMT5 in E.coli. Progress in Biochemistry and Biophysics 35 (7).
39. Wang, X., Zhang, Y., Ma, Q., Zhang, Z., Xue, Y., Bao, S*., and Chong, K*. (2007). SKB1-mediated symmetric dimethylation of histone H4R3 controls flowering time in Arabidopsis. EMBO J. 26, 1934-1941.
40. Hou, X., Wang, Y., Zhou, Z., Bao, S., Lin, Y., and Gong, W. (2007). Crystal structure of SAM-dependent O-methyltransferase from pathogenic bacterium Leptospira interrogans. J Struct Biol 159, 523-528.
41. Liu, Z., Zhou, Z., Chen, G., and Bao, S*. (2007). A putative transcriptional elongation factor hIws1 is essential for mammalian cell proliferation. Biochem Biophys Res Commun 353, 47-53.
42. Wang, X., Xu, Y., Han, Y., Bao, S., Du, J., Yuan, M., Xu, Z., and Chong, K. (2006). Overexpression of RAN1 in rice and Arabidopsis alters primordial meristem, mitotic progress, and sensitivity to auxin. Plant Physiol 140, 91-101.
43. Wang, X., Zou, L., Lu, T., Bao, S., Hurov, K. E., Hittelman, W. N., Elledge, S. J., and Li, L. (2006). Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol Cell 23, 331-341.
44. Cheng, Z., Bao, S., Shan, X., Xu, H., and Gong, W. (2006). Human thioesterase superfamily member 2 (hTHEM2) is co-localized with beta-tubulin onto the microtubule. Biochem Biophys Res Commun 350, 850-853.
45. Bao, S., Lu, T., Wang, X., Zheng, H., Wang, L. E., Wei, Q., Hittelman, W. N., and Li, L. (2004). Disruption of the Rad9/Rad1/Hus1 (9-1-1) complex leads to checkpoint signaling and replication defects. Oncogene 23, 5586-5593.
46. Hu, M. C., Lee, D. F., Xia, W., Golfman, L. S., Ou-Yang, F., Yang, J. Y., Zou, Y., Bao, S., Hanada, N., Saso, H., et al. (2004). IkappaB kinase promotes tumorigenesis through inhibition of forkhead FOXO3a. Cell 117, 225-237.
47. Bao, S., Qyang, Y., Yang, P., Kim, H., Du, H., Bartholomeusz, G., Henkel, J., Pimental, R., Verde, F., and Marcus, S. (2001). The highly conserved protein methyltransferase, Skb1, is a mediator of hyperosmotic stress response in the fission yeast Schizosaccharomyces pombe. J Biol Chem 276, 14549-14552.
48. Kim, H. W., Yang, P., Qyang, Y., Lai, H., Du, H., Henkel, J. S., Kumar, K., Bao, S., Liu, M., and Marcus, S. (2001). Genetic and molecular characterization of Skb15, a highly conserved inhibitor of the fission yeast PAK, Shk1. Mol Cell 7, 1095-1101.
49. Li, H., Sherman, D. M., Bao, S., and Sherman, L. A. (2001). Pattern of cyanophycin accumulation in nitrogen-fixing and non-nitrogen-fixing cyanobacteria. Arch Microbiol 176, 9-18.
