Photo of Yi Zhang,  PhD

Yi Zhang, PhD

Boston Children's Hospital

Boston Children's Hospital
Phone: (617) 713-8666
Fax: (617) 713-8665


yzhang@genetics.med.harvard.edu

Yi Zhang, PhD

Boston Children's Hospital

EDUCATIONAL TITLES

  • Fred Rosen Professor, Genetics, Harvard Medical School
  • Senior Inviestigator, Program in Cellular and Molecular Medicine, Boston Children's Hospital

DF/HCC PROGRAM AFFILIATION

Research Abstract

The major focus of the Zhang lab has been the identification and characterization of the chromatin modifying enzymes that include: (1) the ATP-dependent nucleosome-remodeling and histone deacetylase complex NuRD; (2) various histone methyltransferases, including PRC2 and hDOT1L; (3) the JmjC-family of histone demethylases; (4) histone H2A ubiquitin E3 ligase PRC1; and (5) the Ten Eleven Translocation (Tet) family of 5-methylcytosine dioxygenases. The general approach of the lab involves biochemical purification and functional characterization of the enzymes in vitro and in cell culture, genomic characterization of their locations and effect on transcriptome, followed by biological characterization in mouse models. These studies have uncovered important functions of these enzymes in transcriptional regulation, cell fate reprogramming and the development of various diseases, such as metabolic syndrome and cancers.

In the recent years, the lab has switched the focus from enzyme characterization to understanding role of epigenetic and chromatin modifications in specific biological processes, such as preimplantation development, cancer drug resistance, and drug addiction.

Publications

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  • Wu X, Zhang Y. TET-mediated active DNA demethylation: mechanism, function and beyond. Nat Rev Genet 2017. PubMed
  • Fenouille N, Bassil CF, Ben-Sahra I, Benajiba L, Alexe G, Ramos A, Pikman Y, Conway AS, Burgess MR, Li Q, Luciano F, Auberger P, Galinsky I, DeAngelo DJ, Stone RM, Zhang Y, Perkins AS, Shannon K, Hemann MT, Puissant A, Stegmaier K. The creatine kinase pathway is a metabolic vulnerability in EVI1-positive acute myeloid leukemia. Nat Med 2017. PubMed
  • Wu X, Inoue A, Suzuki T, Zhang Y. Simultaneous mapping of active DNA demethylation and sister chromatid exchange in single cells. Genes Dev 2017; 31:511-523. PubMed
  • Kim M, Lu F, Zhang Y. Loss of HDAC-Mediated Repression and Gain of NF-κB Activation Underlie Cytokine Induction in ARID1A- and PIK3CA-Mutation-Driven Ovarian Cancer. Cell Rep 2016; 17:275-88. PubMed
  • Wu H, Wu X, Zhang Y. Base-resolution profiling of active DNA demethylation using MAB-seq and caMAB-seq. Nat Protoc 2016; 11:1081-100. PubMed
  • Chung YG, Matoba S, Liu Y, Eum JH, Lu F, Jiang W, Lee JE, Sepilian V, Cha KY, Lee DR, Zhang Y. Histone Demethylase Expression Enhances Human Somatic Cell Nuclear Transfer Efficiency and Promotes Derivation of Pluripotent Stem Cells. Cell Stem Cell 2015; 17:758-66. PubMed
  • Wu H, Wu X, Shen L, Zhang Y. Single-base resolution analysis of active DNA demethylation using methylase-assisted bisulfite sequencing. Nat Biotechnol 2014; 32:1231-40. PubMed
  • Matoba S, Liu Y, Lu F, Iwabuchi KA, Shen L, Inoue A, Zhang Y. Embryonic development following somatic cell nuclear transfer impeded by persisting histone methylation. Cell 2014; 159:884-95. PubMed
  • Shen L, Inoue A, He J, Liu Y, Lu F, Zhang Y. Tet3 and DNA replication mediate demethylation of both the maternal and paternal genomes in mouse zygotes. Cell Stem Cell 2014; 15:459-70. PubMed
  • Lu F, Liu Y, Jiang L, Yamaguchi S, Zhang Y. Role of Tet proteins in enhancer activity and telomere elongation. Genes Dev 2014; 28:2103-19. PubMed
  • Inoue A, Zhang Y. Nucleosome assembly is required for nuclear pore complex assembly in mouse zygotes. Nat Struct Mol Biol 2014; 21:609-16. PubMed
  • Wang Y, Zhang Y. Regulation of TET protein stability by calpains. Cell Rep 2014; 6:278-84. PubMed
  • Wu H, Zhang Y. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell 2014; 156:45-68. PubMed
  • Shen L, Song CX, He C, Zhang Y. Mechanism and function of oxidative reversal of DNA and RNA methylation. Annu Rev Biochem 2014; 83:585-614. PubMed
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