Yi Zhang (biochemist) explained

Yi Zhang
Birth Name:Zhang Yi
Birth Place:Chongqing, China
Workplaces:Harvard Medical School
Boston Children's Hospital
Howard Hughes Medical Institute
Academic Advisors:Danny Reinberg
Known For:Epigenetics
Embryogenesis
Somatic cell nuclear transfer
Stem cell
Education:B.Sc. and master's degree in biophysics from China Agricultural University
Ph.D. in molecular biophysics from Florida State University

Yi Zhang 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

External links

Notes and References

  1. Web site: Yi Zhang . Harvard Medical School . 2018-12-10.
  2. Web site: Yi Zhang, PhD . Boston Children's Hospital . 2018-12-10.
  3. Web site: Yi Zhang. HHMI . 2018-12-10.
  4. Web site: Yi Zhang, PhD. hsci.harvard.edu. en. 2018-12-12.
  5. Web site: Our faculty: Associate and affiliate members. 2008-05-08. Broad Institute. en. 2018-12-12.
  6. Web site: 张毅：1美元起步的哈佛讲席教授 . Caixin . 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. 0092-8674. 9150135. 10.1016/s0092-8674(00)80216-0. free.
  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. 0092-8674. 9790534. 10.1016/s0092-8674(00)81758-4. 18786866. free.
  9. Web site: An Epic Search. The Scientist Magazine®. en. 2018-12-16.
  10. Web site: Epizyme targeting cancer sub-populations with small molecule HMT inhibitors. Writer. Michael Flanagan Senior. BioCentury. en. 2018-12-16.
  11. Web site: Yi Zhang named as Kenan Distinguished Professor. 2009-06-04. Biochemistry and Biophysics. en-US. 2018-12-14.
  12. Web site: Yi Zhang - Google Scholar Citations. scholar.google.com. 2018-12-10.
  13. Web site: Sequencing Biology's Hottest, 2002-06 - ScienceWatch.com. archive.sciencewatch.com. 2018-12-10.
  14. Web site: 2014. The World's Most Influential Scientific Minds. 2018-12-10. li.mit.edu.
  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. 10.1126/science.1060781. 0036-8075. 11387442. 33566292. free.
  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. 0960-9822. 12123582. 10.1016/s0960-9822(02)00901-6. 2002CBio...12.1052F . 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. 10.1016/j.cell.2005.02.020. 0092-8674. 15851025. 15638573. free.
  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. 10.1126/science.1076997. 1095-9203. 12351676. 2002Sci...298.1039C. 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. 10.1126/science.1084274. 1095-9203. 12649488. 2003Sci...300..131P. 28578313. free.
  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. 10.1038/ng1467. 1061-4036. 15516932. 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. 10.1038/cr.2010.114. 1748-7838. 2949548. 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. 10.1038/nature02985. 1476-4687. 15386022. 10261/73732. 2004Natur.431..873W. 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. 10.1038/nature04433. 1476-4687. 16362057. 2006Natur.439..811T. 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. 10.1038/nature04853. 1476-4687. 16732292. 2006Natur.442..312K. 4399312.
  25. Okada. Yuki. Scott. Greg. Ray. Manas K.. Mishina. Yuji. Yuji Mishina. Zhang. Yi. 2007-11-01. Histone demethylase JHDM2A is critical for Tnp1 and Prm1 transcription and spermatogenesis. Nature. 450. 7166. 119–123. 10.1038/nature06236. 1476-4687. 17943087. 2007Natur.450..119O. 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. 10.1038/nature07777. 1476-4687. 4085783. 19194461. 2009Natur.458..757T.
  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. 10.1016/j.molcel.2007.03.001. 1097-2765. 17363312. free.
  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. 10.1016/j.cell.2007.02.013. 0092-8674. 17320163. 1412135. free.
  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. 10.1038/ncb2483. 1476-4679. 3544197. 22522173.
  30. 2014-11-06. Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation. Cell. en. 159. 4. 884–895. 10.1016/j.cell.2014.09.055. 25417163. 4243038. 0092-8674. Matoba. Shogo. Liu. Yuting. Lu. Falong. Iwabuchi. Kumiko A.. Shen. Li. Inoue. Azusa. Zhang. Yi.
  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. 10.1016/j.stem.2015.10.001. 1875-9777. 26526725. free.
  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. 10.1016/j.cell.2018.01.020. 1097-4172. 29395327. free.
  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. 10.1038/nature09303. 1476-4687. 3491567. 20639862. 2010Natur.466.1129I.
  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. 10.1126/science.1210597. 1095-9203. 3495246. 21778364. 2011Sci...333.1300I.
  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. 10.1016/j.cell.2013.04.002. 1097-4172. 3687516. 23602152.
  36. Inoue. Azusa. Zhang. Yi. 2011-10-14. Replication-dependent loss of 5-hydroxymethylcytosine in mouse preimplantation embryos. Science. 334. 6053. 194. 10.1126/science.1212483. 1095-9203. 3799877. 21940858. 2011Sci...334..194I.
  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. 10.1016/j.stem.2014.09.002. 1875-9777. 4201500. 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. 10.1038/nature11709. 1476-4687. 3528851. 23151479. 2012Natur.492..443Y.
  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. 10.1038/nature12805. 1476-4687. 3957231. 24291790. 2013Natur.504..460Y.
  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. 10.1038/nsmb.2839. 1545-9985. 24908396. 15363685. 7700014.
  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. 10.1016/j.cell.2016.05.050. 1097-4172. 27259149. 6625655.
  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. 10.1038/nature23262. 1476-4687. 28723896. 9674007 . 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. 10.1101/gad.304113.117. 1549-5477. 5710138. 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. 10.1101/gad.318675.118. 1549-5477. 30463900. 6295166.
  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. 10.1016/j.stem.2018.06.008. 1875-9777. 30033120. 6326833.
  46. News: National Academy of Medicine Elects 100 New Members . 9 October 2023 . National Academy of Medicine . 9 October 2023.
  47. Web site: Historic Fellows. American Association for the Advancement of Science. en. 2018-12-10.
  48. Web site: CBIS Awards . www.cbisociety.org . 2023-03-25 . 2009.
  49. Web site: Yi Zhang named as Kenan Distinguished Professor. 2009-06-04. Biochemistry and Biophysics. en-US. 2018-12-10.
  50. News: UNC Lineberger scientist receives first-ever Battle Research Award — UNC School of Medicine. 2018-12-10.
  51. News: Four faculty members are honored with Hettleman Prize; chancellor to recognize them at Friday Faculty Council — News Room - UNC Health Care. 2018-12-10.
  52. Web site: Grants Awarded for 2000 • V Foundation. V Foundation. en-US. 2018-12-10.

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