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Yi Zhang (biochemist)

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The native form of this personal name is Zhang Yi. This article uses Western name order when mentioning individuals.
Yi Zhang
Born
Zhang Yi

Chongqing, China
EducationB.Sc. and master's degree in biophysics from China Agricultural University
Ph.D. in molecular biophysics from Florida State University
Known forEpigenetics
Embryogenesis
Somatic cell nuclear transfer
Stem cell
Scientific career
InstitutionsHarvard Medical School
Boston Children's Hospital
Howard Hughes Medical Institute
Academic advisorsDanny Reinberg
Websitewww.zhanglab.tch.harvard.edu

Yi Zhang (Chinese: 张毅; pinyin: Zhāng Yì) is a Chinese-American biochemist who specializes in the fields of epigenetics, chromatin, and developmental reprogramming. He is a Fred Rosen Professor of Pediatrics and professor of genetics at Harvard Medical School,[1] a senior investigator of Program in Cellular and Molecular Medicine at Boston Children's Hospital,[2] and an investigator of the Howard Hughes Medical Institute.[3] He is also an associate member of the Harvard Stem Cell Institute,[4] as well as the Broad Institute of MIT and Harvard.[5] He is best known for his discovery of several classes of epigenetic enzymes and the identification of epigenetic barriers of SCNT cloning.

Education

Zhang received his B.Sc. and master's degrees in biophysics from China Agricultural University in 1984 and 1987, respectively. He then received his Ph.D. in molecular biophysics from Florida State University in 1995.[6] From 1995 to 1999, He did his postdoctoral training in the lab of Danny Reinberg at the Howard Hughes Medical Institute, Robert Wood Johnson Medical School of the University of Medicine and Dentistry of New Jersey.[7][8]

Career and research

Appointments

Research

Zhang has published more than 180 highly influential papers. These studies have been cited over 88,000 times (H-index 121),[12] making him one of the top 10 authors of high impact papers in the fields of molecular biology and genetics[13] (ScienceWatch 2008), and one of the "most influential scientific minds"[14] (ScienceWatch 2014). He was also a Founder of Epizyme, and NewStem (Natick, MA). His current efforts are focused on the molecular mechanism of embryonic development & reprogramming, brain reward-related learning & memory, pancreatic cancer.

Zhang has made several landmark discoveries in the fields of epigenetics, chromatin and developmental reprogramming.

  1. Zhang was the first to systematically identify and characterize six histone methyltransferases, including the H4R3 methyltransferase PRMT1,[15] the H3K79 methyltransferase Dot1L,[16][17] and the H3K27me3 methyltransferase EZH2/PRC2.[18] He went on to demonstrate the function of H3K27me3 methylation in X chromosome inactivation,[19] genomic imprinting,[20] and non-coding RNA regulation.[21] He was also the first to uncover PRC1 as an E3 ligase mediating H2A ubiquitylation.[22] By discovering two enzymatic activities of two PcG protein complexes, Zhang has contributed significantly to our current understanding of the PcG silencing mechanism.
  2. Zhang was the first to show JmjC domain is a signature motif for histone demethylases.[23] He not only worked out the demethylation mechanism, but also demonstrated that JmjC demethylases can demethylate trimethyl state.[24] Zhang went on to show the diverse function of histone demethylases in spermatogenesis,[25] metabolism,[26] cancer,[27][28] iPSC generation,[29] and somatic cell nuclear transfer reprogramming.[30][31] The last finding overcomes a major barrier in SCNT cloning, contributing to the success of the first primate cloning by a team of Chinese scientists[32]
  3. Zhang not only discovered 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) in mammalian genomic DNA, but also elucidated the DNA demethylation mechanism by demonstrating that Tet proteins can sequentially oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC),[33] 5fC, and 5caC[34] in a cyclic manner in mouse embryonic stem cells.[35] He continued to reveal the function of Tet proteins in zygotic DNA demethylation,[36][37] germ cell development,[38] and genomic imprinting erasure[39]
  4. Zhang contributed to the understanding of the molecular events during mammalian embryogenesis by uncovering an important function of de novo nucleosome assembly in nuclear pore complex formation,[40] identifying key factors for zygotic genome activation,[41] revealing a new mechanism of genomic imprinting[42] and imprinted X-inactivation,[43][44] as well as the role of this new imprinting mechanism in SCNT cloning[45]

Honors and recognition

References

  1. ^ a b "Yi Zhang". Harvard Medical School. Retrieved 2018-12-10.
  2. ^ a b "Yi Zhang, PhD". Boston Children's Hospital. Retrieved 2018-12-10.
  3. ^ a b c "Yi Zhang". HHMI. Retrieved 2018-12-10.
  4. ^ "Yi Zhang, PhD". hsci.harvard.edu. Retrieved 2018-12-12.
  5. ^ "Our faculty: Associate and affiliate members". Broad Institute. 2008-05-08. Retrieved 2018-12-12.
  6. ^ "张毅：1美元起步的哈佛讲席教授". Caixin. Retrieved 2018-12-14.
  7. ^ Zhang, Y.; Iratni, R.; Erdjument-Bromage, H.; Tempst, P.; Reinberg, D. (1997-05-02). "Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex". Cell. 89 (3): 357–364. doi:10.1016/s0092-8674(00)80216-0. ISSN 0092-8674. PMID 9150135.
  8. ^ Zhang, Y.; LeRoy, G.; Seelig, H. P.; Lane, W. S.; Reinberg, D. (1998-10-16). "The dermatomyositis-specific autoantigen Mi2 is a component of a complex containing histone deacetylase and nucleosome remodeling activities". Cell. 95 (2): 279–289. doi:10.1016/s0092-8674(00)81758-4. ISSN 0092-8674. PMID 9790534. S2CID 18786866.
  9. ^ "An Epic Search". The Scientist Magazine®. Retrieved 2018-12-16.
  10. ^ Writer, Michael Flanagan Senior. "Epizyme targeting cancer sub-populations with small molecule HMT inhibitors". BioCentury. Retrieved 2018-12-16.
  11. ^ "Yi Zhang named as Kenan Distinguished Professor". Biochemistry and Biophysics. 2009-06-04. Retrieved 2018-12-14.
  12. ^ "Yi Zhang - Google Scholar Citations". scholar.google.com. Retrieved 2018-12-10.
  13. ^ a b "Sequencing Biology's Hottest, 2002-06 - ScienceWatch.com". archive.sciencewatch.com. Retrieved 2018-12-10.
  14. ^ "The World's Most Influential Scientific Minds" (PDF). li.mit.edu. 2014. Retrieved 2018-12-10.
  15. ^ Wang, H.; Huang, Z. Q.; Xia, L.; Feng, Q.; Erdjument-Bromage, H.; Strahl, B. D.; Briggs, S. D.; Allis, C. D.; Wong, J. (2001-08-03). "Methylation of histone H4 at arginine 3 facilitating transcriptional activation by nuclear hormone receptor". Science. 293 (5531): 853–857. doi:10.1126/science.1060781. ISSN 0036-8075. PMID 11387442. S2CID 33566292.
  16. ^ Feng, Qin; Wang, Hengbin; Ng, Huck Hui; Erdjument-Bromage, Hediye; Tempst, Paul; Struhl, Kevin; Zhang, Yi (2002-06-25). "Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain". Current Biology. 12 (12): 1052–1058. Bibcode:2002CBio...12.1052F. doi:10.1016/s0960-9822(02)00901-6. ISSN 0960-9822. PMID 12123582. S2CID 17263035.
  17. ^ Okada, Yuki; Feng, Qin; Lin, Yihui; Jiang, Qi; Li, Yaqiang; Coffield, Vernon M.; Su, Lishan; Xu, Guoliang; Zhang, Yi (2005-04-22). "hDOT1L links histone methylation to leukemogenesis". Cell. 121 (2): 167–178. doi:10.1016/j.cell.2005.02.020. ISSN 0092-8674. PMID 15851025. S2CID 15638573.
  18. ^ Cao, Ru; Wang, Liangjun; Wang, Hengbin; Xia, Li; Erdjument-Bromage, Hediye; Tempst, Paul; Jones, Richard S.; Zhang, Yi (2002-11-01). "Role of histone H3 lysine 27 methylation in Polycomb-group silencing". Science. 298 (5595): 1039–1043. Bibcode:2002Sci...298.1039C. doi:10.1126/science.1076997. ISSN 1095-9203. PMID 12351676. S2CID 6265267.
  19. ^ Plath, Kathrin; Fang, Jia; Mlynarczyk-Evans, Susanna K.; Cao, Ru; Worringer, Kathleen A.; Wang, Hengbin; de la Cruz, Cecile C.; Otte, Arie P.; Panning, Barbara (2003-04-04). "Role of histone H3 lysine 27 methylation in X inactivation". Science. 300 (5616): 131–135. Bibcode:2003Sci...300..131P. doi:10.1126/science.1084274. ISSN 1095-9203. PMID 12649488. S2CID 28578313.
  20. ^ Umlauf, David; Goto, Yuji; Cao, Ru; Cerqueira, Frédérique; Wagschal, Alexandre; Zhang, Yi; Feil, Robert (December 2004). "Imprinting along the Kcnq1 domain on mouse chromosome 7 involves repressive histone methylation and recruitment of Polycomb group complexes". Nature Genetics. 36 (12): 1296–1300. doi:10.1038/ng1467. ISSN 1061-4036. PMID 15516932. S2CID 19084498.
  21. ^ Wu, Susan C.; Kallin, Eric M.; Zhang, Yi (October 2010). "Role of H3K27 methylation in the regulation of lncRNA expression". Cell Research. 20 (10): 1109–1116. doi:10.1038/cr.2010.114. ISSN 1748-7838. PMC 2949548. PMID 20680032.
  22. ^ Wang, Hengbin; Wang, Liangjun; Erdjument-Bromage, Hediye; Vidal, Miguel; Tempst, Paul; Jones, Richard S.; Zhang, Yi (2004-10-14). "Role of histone H2A ubiquitination in Polycomb silencing". Nature. 431 (7010): 873–878. Bibcode:2004Natur.431..873W. doi:10.1038/nature02985. hdl:10261/73732. ISSN 1476-4687. PMID 15386022. S2CID 4344378.
  23. ^ Tsukada, Yu-ichi; Fang, Jia; Erdjument-Bromage, Hediye; Warren, Maria E.; Borchers, Christoph H.; Tempst, Paul; Zhang, Yi (2006-02-16). "Histone demethylation by a family of JmjC domain-containing proteins". Nature. 439 (7078): 811–816. Bibcode:2006Natur.439..811T. doi:10.1038/nature04433. ISSN 1476-4687. PMID 16362057. S2CID 4415889.
  24. ^ Klose, Robert J.; Yamane, Kenichi; Bae, Yangjin; Zhang, Dianzheng; Erdjument-Bromage, Hediye; Tempst, Paul; Wong, Jiemin; Zhang, Yi (2006-07-20). "The transcriptional repressor JHDM3A demethylates trimethyl histone H3 lysine 9 and lysine 36". Nature. 442 (7100): 312–316. Bibcode:2006Natur.442..312K. doi:10.1038/nature04853. ISSN 1476-4687. PMID 16732292. S2CID 4399312.
  25. ^ Okada, Yuki; Scott, Greg; Ray, Manas K.; Mishina, Yuji; Zhang, Yi (2007-11-01). "Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis". Nature. 450 (7166): 119–123. Bibcode:2007Natur.450..119O. doi:10.1038/nature06236. ISSN 1476-4687. PMID 17943087. S2CID 4387658.
  26. ^ Tateishi, Keisuke; Okada, Yuki; Kallin, Eric M.; Zhang, Yi (2009-04-09). "Role of Jhdm2a in regulating metabolic gene expression and obesity resistance". Nature. 458 (7239): 757–761. Bibcode:2009Natur.458..757T. doi:10.1038/nature07777. ISSN 1476-4687. PMC 4085783. PMID 19194461.
  27. ^ Yamane, Kenichi; Tateishi, Keisuke; Klose, Robert J.; Fang, Jia; Fabrizio, Laura A.; Erdjument-Bromage, Hediye; Taylor-Papadimitriou, Joyce; Tempst, Paul; Zhang, Yi (2007-03-23). "PLU-1 is an H3K4 demethylase involved in transcriptional repression and breast cancer cell proliferation". Molecular Cell. 25 (6): 801–812. doi:10.1016/j.molcel.2007.03.001. ISSN 1097-2765. PMID 17363312.
  28. ^ Klose, Robert J.; Yan, Qin; Tothova, Zuzana; Yamane, Kenichi; Erdjument-Bromage, Hediye; Tempst, Paul; Gilliland, D. Gary; Zhang, Yi; Kaelin, William G. (2007-03-09). "The retinoblastoma binding protein RBP2 is an H3K4 demethylase". Cell. 128 (5): 889–900. doi:10.1016/j.cell.2007.02.013. ISSN 0092-8674. PMID 17320163. S2CID 1412135.
  29. ^ Liang, Gaoyang; He, Jin; Zhang, Yi (2012-04-22). "Kdm2b promotes induced pluripotent stem cell generation by facilitating gene activation early in reprogramming". Nature Cell Biology. 14 (5): 457–466. doi:10.1038/ncb2483. ISSN 1476-4679. PMC 3544197. PMID 22522173.
  30. ^ Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Azusa; Zhang, Yi (2014-11-06). "Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation". Cell. 159 (4): 884–895. doi:10.1016/j.cell.2014.09.055. ISSN 0092-8674. PMC 4243038. PMID 25417163.
  31. ^ Chung, Young Gie; Matoba, Shogo; Liu, Yuting; Eum, Jin Hee; Lu, Falong; Jiang, Wei; Lee, Jeoung Eun; Sepilian, Vicken; Cha, Kwang Yul (2015-12-03). "Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells". Cell Stem Cell. 17 (6): 758–766. doi:10.1016/j.stem.2015.10.001. ISSN 1875-9777. PMID 26526725.
  32. ^ Liu, Zhen; Cai, Yijun; Wang, Yan; Nie, Yanhong; Zhang, Chenchen; Xu, Yuting; Zhang, Xiaotong; Lu, Yong; Wang, Zhanyang (2018-02-08). "Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer". Cell. 172 (4): 881–887.e7. doi:10.1016/j.cell.2018.01.020. ISSN 1097-4172. PMID 29395327.
  33. ^ Ito, Shinsuke; D'Alessio, Ana C.; Taranova, Olena V.; Hong, Kwonho; Sowers, Lawrence C.; Zhang, Yi (2010-08-26). "Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification". Nature. 466 (7310): 1129–1133. Bibcode:2010Natur.466.1129I. doi:10.1038/nature09303. ISSN 1476-4687. PMC 3491567. PMID 20639862.
  34. ^ Ito, Shinsuke; Shen, Li; Dai, Qing; Wu, Susan C.; Collins, Leonard B.; Swenberg, James A.; He, Chuan; Zhang, Yi (2011-09-02). "Tet proteins can convert 5-methylcytosine to 5-formylcytosine and 5-carboxylcytosine". Science. 333 (6047): 1300–1303. Bibcode:2011Sci...333.1300I. doi:10.1126/science.1210597. ISSN 1095-9203. PMC 3495246. PMID 21778364.
  35. ^ Shen, Li; Wu, Hao; Diep, Dinh; Yamaguchi, Shinpei; D'Alessio, Ana C.; Fung, Ho-Lim; Zhang, Kun; Zhang, Yi (2013-04-25). "Genome-wide analysis reveals TET- and TDG-dependent 5-methylcytosine oxidation dynamics". Cell. 153 (3): 692–706. doi:10.1016/j.cell.2013.04.002. ISSN 1097-4172. PMC 3687516. PMID 23602152.
  36. ^ Inoue, Azusa; Zhang, Yi (2011-10-14). "Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos". Science. 334 (6053): 194. Bibcode:2011Sci...334..194I. doi:10.1126/science.1212483. ISSN 1095-9203. PMC 3799877. PMID 21940858.
  37. ^ Shen, Li; Inoue, Azusa; He, Jin; Liu, Yuting; Lu, Falong; Zhang, Yi (2014-10-02). "Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes". Cell Stem Cell. 15 (4): 459–471. doi:10.1016/j.stem.2014.09.002. ISSN 1875-9777. PMC 4201500. PMID 25280220.
  38. ^ Yamaguchi, Shinpei; Hong, Kwonho; Liu, Rui; Shen, Li; Inoue, Azusa; Diep, Dinh; Zhang, Kun; Zhang, Yi (2012-12-20). "Tet1 controls meiosis by regulating meiotic gene expression". Nature. 492 (7429): 443–447. Bibcode:2012Natur.492..443Y. doi:10.1038/nature11709. ISSN 1476-4687. PMC 3528851. PMID 23151479.
  39. ^ Yamaguchi, Shinpei; Shen, Li; Liu, Yuting; Sendler, Damian; Zhang, Yi (2013-12-19). "Role of Tet1 in erasure of genomic imprinting". Nature. 504 (7480): 460–464. Bibcode:2013Natur.504..460Y. doi:10.1038/nature12805. ISSN 1476-4687. PMC 3957231. PMID 24291790.
  40. ^ Inoue, Azusa; Zhang, Yi (July 2014). "Nucleosome assembly is required for nuclear pore complex assembly in mouse zygotes". Nature Structural & Molecular Biology. 21 (7): 609–616. doi:10.1038/nsmb.2839. ISSN 1545-9985. PMC 7700014. PMID 24908396. S2CID 15363685.
  41. ^ Lu, Falong; Liu, Yuting; Inoue, Azusa; Suzuki, Tsukasa; Zhao, Keji; Zhang, Yi (2016-06-02). "Establishing Chromatin Regulatory Landscape during Mouse Preimplantation Development". Cell. 165 (6): 1375–1388. doi:10.1016/j.cell.2016.05.050. ISSN 1097-4172. PMC 6625655. PMID 27259149.
  42. ^ Inoue, Azusa; Jiang, Lan; Lu, Falong; Suzuki, Tsukasa; Zhang, Yi (27 July 2017). "Maternal H3K27me3 controls DNA methylation-independent imprinting". Nature. 547 (7664): 419–424. doi:10.1038/nature23262. ISSN 1476-4687. PMC 9674007. PMID 28723896. S2CID 3418391.
  43. ^ Inoue, Azusa; Jiang, Lan; Lu, Falong; Zhang, Yi (1 October 2017). "Genomic imprinting of Xist by maternal H3K27me3". Genes & Development. 31 (19): 1927–1932. doi:10.1101/gad.304113.117. ISSN 1549-5477. PMC 5710138. PMID 29089420.
  44. ^ Inoue, Azusa; Chen, Zhiyuan; Yin, Qiangzong; Zhang, Yi (1 December 2018). "Maternal Eed knockout causes loss of H3K27me3 imprinting and random X inactivation in the extraembryonic cells". Genes & Development. 32 (23–24): 1525–1536. doi:10.1101/gad.318675.118. ISSN 1549-5477. PMC 6295166. PMID 30463900.
  45. ^ Matoba, Shogo; Wang, Huihan; Jiang, Lan; Lu, Falong; Iwabuchi, Kumiko A.; Wu, Xiaoji; Inoue, Kimiko; Yang, Lin; Press, William (2018-09-06). "Loss of H3K27me3 Imprinting in Somatic Cell Nuclear Transfer Embryos Disrupts Post-Implantation Development". Cell Stem Cell. 23 (3): 343–354.e5. doi:10.1016/j.stem.2018.06.008. ISSN 1875-9777. PMC 6326833. PMID 30033120.
  46. ^ "National Academy of Medicine Elects 100 New Members". National Academy of Medicine. 9 October 2023. Retrieved 9 October 2023.
  47. ^ "Historic Fellows". American Association for the Advancement of Science. Retrieved 2018-12-10.
  48. ^ "CBIS Awards" (PDF). www.cbisociety.org. 2009. Retrieved 2023-03-25.
  49. ^ "Yi Zhang named as Kenan Distinguished Professor". Biochemistry and Biophysics. 2009-06-04. Retrieved 2018-12-10.
  50. ^ "UNC Lineberger scientist receives first-ever Battle Research Award — UNC School of Medicine". Retrieved 2018-12-10.
  51. ^ "Four faculty members are honored with Hettleman Prize; chancellor to recognize them at Friday Faculty Council — News Room - UNC Health Care". Retrieved 2018-12-10.
  52. ^ "Grants Awarded for 2000 • V Foundation". V Foundation. Retrieved 2018-12-10.
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