Research

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Yang  Shi, PhD

Yang Shi PhD
Lab:
Shi Laboratory
Program:
Neurobiology Program
Department:
Medicine Research
Division
Newborn Medicine Research
Hospital Title:
Merton Bernfield Professor of Neonatology
Academic Title:
Professor of Cell Biology; Professor of Pediatrics, Harvard Medical School
Research Focus Area:
Epigenetic mechanisms
Contact:
617-919-3100
Contact Via Email
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Research Overview

Histone N-terminal tails are extensively modified by a plethora of post-translational modifications, including histone methylation. Histone methylation has been implicated in multiple biological processes including heterochromatin formation, Xinactivation, genomic imprinting and silencing of homeotic genes. Methylation occurs on both lysine (K) and arginine (R) residues. Multiple K residues on the tails of histone H3 and H4 have been shown to be sites for methylation (mono-, di, and tri-methylation). Methylation at these sites has been linked to transcriptional activation and repression, as well as DNA damage response, indicating a widespread role for histone methylation in various aspects of chromatin biology. Unlike other histone modifications such as acetylation, methylation has long been considered a “permanent” modification. Our identification of the first histone demethylase LSD1 disproved this dogma, and suggested that histone methylation is dynamically regulated by both histone methylases and demethylases. Importantly, we have recently identified another large family of new histone demethylases (JmjC) that specialize in demethylating lysine trimethylation. Collectively these findings suggest that all three methylation states of the lysine residue (mono-, di- and trimethylation) can be reversed enzymatically. Our findings firmly established the notion that histone methylation is dynamically regulated by both histone methylases and demethylases. We are currently addressing the issues of mechanisms and biology of these newly identified histone demethylases in genetically tractable model organisms such as S. pombe, C. elegans and zebrafish. We are also exploring potential disease connections of these newly identified chromatin regulators. Finally, we are continuing our screens for new histone demethylases and are also using the assays established in the lab to search for potential DNA demethylases.

What are the functions of the various modifications that take place on the histone tails? One model suggests that these modifications (or lack thereof) serve as platforms for the recruitment of additional regulatory machineries that impact local chromatin structure and function. In fact, cells have dedicated significant resources to developing ways of recognizing histone tail modifications as evidenced by the recent identification of multiple protein modalities dedicated to recognizing various histone methylation marks. A challenge is to understand how combinatorial modifications on the histone tails are recognized, which is another area of focus of our lab. About Yang Shi Yang Shi joined Harvard Medical School as an assistant professor in 1991 and was appointed a Professor of Pathology in 2004. He is currently a Professor of Cell Biology. He is also the Merton Bernfield Professor of Neonatology in the Division of Newborn Medicine at Children’s Hospital Boston. Yang Shi received his PhD from NYU and postdoctoral training at Princeton University.

About Yang Shi

Yang Shi joined Harvard Medical School as an assistant professor in 1991 and was appointed a Professor of Pathology in 2004. He is currently a Professor of Cell Biology. He is also the Merton Bernfield Professor of Neonatology in the Division of Newborn Medicine at Children’s Hospital Boston. Yang Shi received his PhD from NYU and postdoctoral training at Princeton University.

 

Publications

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  1. Sendinc E, Jambhekar A, Shi Y. Remodeling Your Way out of Cell Cycle. Cell. 2015 Jul 16; 162(2):237-8.
  2. Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y. DNA Methylation on N6-Adenine in C. elegans. Cell. 2015 May 7; 161(4):868-78.
  3. Murn J, Zarnack K, Yang YJ, Durak O, Murphy EA, Cheloufi S, Gonzalez DM, Teplova M, Curk T, Zuber J, Patel DJ, Ule J, Luscombe NM, Tsai LH, Walsh CA, Shi Y. Control of a neuronal morphology program by an RNA-binding zinc finger protein, Unkempt. Genes Dev. 2015 Mar 1; 29(5):501-12.
  4. Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y. A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Mol Cell. 2015 Mar 19; 57(6):957-70.
  5. Brookes E, Laurent B, Õunap K, Carroll R, Moeschler JB, Field M, Schwartz CE, Gecz J, Shi Y. Mutations in the intellectual disability gene KDM5C reduce protein stability and demethylase activity. Hum Mol Genet. 2015 May 15; 24(10):2861-72.
  6. Lan F, Shi Y. Histone H3.3 and cancer: A potential reader connection. Proc Natl Acad Sci U S A. 2015 Jun 2; 112(22):6814-9.
  7. Brookes E, Shi Y. Diverse epigenetic mechanisms of human disease. Annu Rev Genet. 2014; 48:237-68.
  8. Greer EL, Beese-Sims SE, Brookes E, Spadafora R, Zhu Y, Rothbart SB, Aristizábal-Corrales D, Chen S, Badeaux AI, Jin Q, Wang W, Strahl BD, Colaiácovo MP, Shi Y. A histone methylation network regulates transgenerational epigenetic memory in C. elegans. Cell Rep. 2014 Apr 10; 7(1):113-26.
  9. Greer EL, Shi Y. What's the Mtrr with your grandparents? Cell Metab. 2013 Oct 1; 18(4):457-9.
  10. Badeaux AI, Shi Y. Emerging roles for chromatin as a signal integration and storage platform. Nat Rev Mol Cell Biol. 2013 Apr; 14(4):211-24.
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  12. Badeaux AI, Shi Y. Emerging roles for chromatin as a signal integration and storage platform. Nat Rev Mol Cell Biol. 2013 Apr; 14(4):211-24.
  13. Yang YJ, Baltus AE, Mathew RS, Murphy EA, Evrony GD, Gonzalez DM, Wang EP, Marshall-Walker CA, Barry BJ, Murn J, Tatarakis A, Mahajan MA, Samuels HH, Shi Y, Golden JA, Mahajnah M, Shenhav R, Walsh CA. Microcephaly gene links trithorax and REST/NRSF to control neural stem cell proliferation and differentiation. Cell. 2012 Nov 21; 151(5):1097-112.
  14. Chen S, Shi Y. A new horizon for epigenetic medicine? Cell Res. 2013 Mar; 23(3):326-8.
  15. Kim HG, Kim HT, Leach NT, Lan F, Ullmann R, Silahtaroglu A, Kurth I, Nowka A, Seong IS, Shen Y, Talkowski ME, Ruderfer D, Lee JH, Glotzbach C, Ha K, Kjaergaard S, Levin AV, Romeike BF, Kleefstra T, Bartsch O, Elsea SH, Jabs EW, MacDonald ME, Harris DJ, Quade BJ, Ropers HH, Shaffer LG, Kutsche K, Layman LC, Tommerup N, Kalscheuer VM, Shi Y, Morton CC, Kim CH, Gusella JF. Translocations disrupting PHF21A in the Potocki-Shaffer-syndrome region are associated with intellectual disability and craniofacial anomalies. Am J Hum Genet. 2012 Jul 13; 91(1):56-72.
  16. Blättler SM, Verdeguer F, Liesa M, Cunningham JT, Vogel RO, Chim H, Liu H, Romanino K, Shirihai OS, Vazquez F, Rüegg MA, Shi Y, Puigserver P. Defective mitochondrial morphology and bioenergetic function in mice lacking the transcription factor Yin Yang 1 in skeletal muscle. Mol Cell Biol. 2012 Aug; 32(16):3333-46.
  17. Chen S, Ma J, Wu F, Xiong LJ, Ma H, Xu W, Lv R, Li X, Villen J, Gygi SP, Liu XS, Shi Y. The histone H3 Lys 27 demethylase JMJD3 regulates gene expression by impacting transcriptional elongation. Genes Dev. 2012 Jun 15; 26(12):1364-75.
  18. Greer EL, Shi Y. Histone methylation: a dynamic mark in health, disease and inheritance. Nat Rev Genet. 2012 Apr 03; 13(5):343-57.
  19. Nottke AC, Beese-Sims SE, Pantalena LF, Reinke V, Shi Y, Colaiácovo MP. SPR-5 is a histone H3K4 demethylase with a role in meiotic double-strand break repair. Proc Natl Acad Sci U S A. 2011 Aug 2; 108(31):12805-10.
  20. Iwase S, Xiang B, Ghosh S, Ren T, Lewis PW, Cochrane JC, Allis CD, Picketts DJ, Patel DJ, Li H, Shi Y. ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome. Nat Struct Mol Biol. 2011 Jun 12; 18(7):769-76.
  21. Rahman S, Sowa ME, Ottinger M, Smith JA, Shi Y, Harper JW, Howley PM. The Brd4 extraterminal domain confers transcription activation independent of pTEFb by recruiting multiple proteins, including NSD3. Mol Cell Biol. 2011 Jul; 31(13):2641-52.
  22. Iwase S, Shi Y. Histone and DNA modifications in mental retardation. Prog Drug Res. 2011; 67:147-73.
  23. Mosammaparast N, Shi Y. Reversal of histone methylation: biochemical and molecular mechanisms of histone demethylases. Annu Rev Biochem. 2010; 79:155-79.
  24. Wang B, Li S, Qi HH, Chowdhury D, Shi Y, Novina CD. Distinct passenger strand and mRNA cleavage activities of human Argonaute proteins. Nat Struct Mol Biol. 2009 Dec; 16(12):1259-66.
  25. Wu S, Hu YC, Liu H, Shi Y. Loss of YY1 impacts the heterochromatic state and meiotic double-strand breaks during mouse spermatogenesis. Mol Cell Biol. 2009 Dec; 29(23):6245-56.
  26. Chen S, Whetstine JR, Ghosh S, Hanover JA, Gali RR, Grosu P, Shi Y. The conserved NAD(H)-dependent corepressor CTBP-1 regulates Caenorhabditis elegans life span. Proc Natl Acad Sci U S A. 2009 Feb 3; 106(5):1496-501.
  27. Mulligan P, Westbrook TF, Ottinger M, Pavlova N, Chang B, Macia E, Shi YJ, Barretina J, Liu J, Howley PM, Elledge SJ, Shi Y. CDYL bridges REST and histone methyltransferases for gene repression and suppression of cellular transformation. Mol Cell. 2008 Dec 5; 32(5):718-26.
  28. Kim HG, Kurth I, Lan F, Meliciani I, Wenzel W, Eom SH, Kang GB, Rosenberger G, Tekin M, Ozata M, Bick DP, Sherins RJ, Walker SL, Shi Y, Gusella JF, Layman LC. Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2008 Oct; 83(4):511-9.
  29. Shi Y. Histone lysine demethylases: emerging roles in development, physiology and disease. Nat Rev Genet. 2007 Nov; 8(11):829-33.
  30. Lan F, Bayliss PE, Rinn JL, Whetstine JR, Wang JK, Chen S, Iwase S, Alpatov R, Issaeva I, Canaani E, Roberts TM, Chang HY, Shi Y. A histone H3 lysine 27 demethylase regulates animal posterior development. Nature. 2007 Oct 11; 449(7163):689-94.
  31. Huarte M, Lan F, Kim T, Vaughn MW, Zaratiegui M, Martienssen RA, Buratowski S, Shi Y. The fission yeast Jmj2 reverses histone H3 Lysine 4 trimethylation. J Biol Chem. 2007 Jul 27; 282(30):21662-70.
  32. Lan F, Zaratiegui M, Villén J, Vaughn MW, Verdel A, Huarte M, Shi Y, Gygi SP, Moazed D, Martienssen RA, Shi Y. S. pombe LSD1 homologs regulate heterochromatin propagation and euchromatic gene transcription. Mol Cell. 2007 Apr 13; 26(1):89-101.
  33. Shi Y, Whetstine JR. Dynamic regulation of histone lysine methylation by demethylases. Mol Cell. 2007 Jan 12; 25(1):1-14.
  34. Luke MP, Sui G, Liu H, Shi Y. Yin Yang 1 physically interacts with Hoxa11 and represses Hoxa11-dependent transcription. J Biol Chem. 2006 Nov 3; 281(44):33226-32.
  35. Affar el B, Gay F, Shi Y, Liu H, Huarte M, Wu S, Collins T, Li E, Shi Y. Essential dosage-dependent functions of the transcription factor yin yang 1 in late embryonic development and cell cycle progression. Mol Cell Biol. 2006 May; 26(9):3565-81.
  36. Whetstine JR, Nottke A, Lan F, Huarte M, Smolikov S, Chen Z, Spooner E, Li E, Zhang G, Colaiacovo M, Shi Y. Reversal of histone lysine trimethylation by the JMJD2 family of histone demethylases. Cell. 2006 May 5; 125(3):467-81.
  37. Affar el B, Luke MP, Gay F, Calvo D, Sui G, Weiss RS, Li E, Shi Y. Targeted ablation of Par-4 reveals a cell type-specific susceptibility to apoptosis-inducing agents. Cancer Res. 2006 Apr 1; 66(7):3456-62.
  38. Rosendorff A, Sakakibara S, Lu S, Kieff E, Xuan Y, DiBacco A, Shi Y, Shi Y, Gill G. NXP-2 association with SUMO-2 depends on lysines required for transcriptional repression. Proc Natl Acad Sci U S A. 2006 Apr 4; 103(14):5308-13.
  39. Liu LP, Ni JQ, Shi YD, Oakeley EJ, Sun FL. Sex-specific role of Drosophila melanogaster HP1 in regulating chromatin structure and gene transcription. Nat Genet. 2005 Dec; 37(12):1361-6.
  40. Shi YJ, Matson C, Lan F, Iwase S, Baba T, Shi Y. Regulation of LSD1 histone demethylase activity by its associated factors. Mol Cell. 2005 Sep 16; 19(6):857-64.
  41. Park SK, Nguyen MD, Fischer A, Luke MP, Affar el B, Dieffenbach PB, Tseng HC, Shi Y, Tsai LH. Par-4 links dopamine signaling and depression. Cell. 2005 Jul 29; 122(2):275-87.
  42. Whetstine JR, Ceron J, Ladd B, Dufourcq P, Reinke V, Shi Y. Regulation of tissue-specific and extracellular matrix-related genes by a class I histone deacetylase. Mol Cell. 2005 May 13; 18(4):483-90.
  43. Sui G, Shi Y. Gene silencing by a DNA vector-based RNAi technology. Methods Mol Biol. 2005; 309:205-18.
  44. Shi Y, Lan F, Matson C, Mulligan P, Whetstine JR, Cole PA, Casero RA, Shi Y. Histone demethylation mediated by the nuclear amine oxidase homolog LSD1. Cell. 2004 Dec 29; 119(7):941-53.
  45. Alpatov R, Munguba GC, Caton P, Joo JH, Shi Y, Shi Y, Hunt ME, Sugrue SP. Nuclear speckle-associated protein Pnn/DRS binds to the transcriptional corepressor CtBP and relieves CtBP-mediated repression of the E-cadherin gene. Mol Cell Biol. 2004 Dec; 24(23):10223-35.
  46. Xiang R, Shi Y, Dillon DA, Negin B, Horváth C, Wilkins JA. 2D LC/MS analysis of membrane proteins from breast cancer cell lines MCF7 and BT474. J Proteome Res. 2004 Nov-Dec; 3(6):1278-83.
  47. Shi Y, Shi Y. Metabolic enzymes and coenzymes in transcription--a direct link between metabolism and transcription? Trends Genet. 2004 Sep; 20(9):445-52.
  48. Chen J, Wall NR, Kocher K, Duclos N, Fabbro D, Neuberg D, Griffin JD, Shi Y, Gilliland DG. Stable expression of small interfering RNA sensitizes TEL-PDGFbetaR to inhibition with imatinib or rapamycin. J Clin Invest. 2004 Jun; 113(12):1784-91.
  49. Lo MC, Gay F, Odom R, Shi Y, Lin R. Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans. Cell. 2004 Apr 2; 117(1):95-106.
  50. Walker AK, Shi Y, Blackwell TK. An extensive requirement for transcription factor IID-specific TAF-1 in Caenorhabditis elegans embryonic transcription. J Biol Chem. 2004 Apr 9; 279(15):15339-47.
  51. Lin X, Liang YY, Sun B, Liang M, Shi Y, Brunicardi FC, Shi Y, Feng XH. Smad6 recruits transcription corepressor CtBP to repress bone morphogenetic protein-induced transcription. Mol Cell Biol. 2003 Dec; 23(24):9081-93.
  52. Shi Y, Blackwell TK. A two-tiered transcription regulation mechanism that protects germ cell identity. Mol Cell. 2003 Nov; 12(5):1062-4.
  53. Wall NR, Shi Y. Small RNA: can RNA interference be exploited for therapy? Lancet. 2003 Oct 25; 362(9393):1401-3.
  54. Brooks JT, Shapiro RL, Kumar L, Wells JG, Phillips-Howard PA, Shi YP, Vulule JM, Hoekstra RM, Mintz E, Slutsker L. Epidemiology of sporadic bloody diarrhea in rural Western Kenya. Am J Trop Med Hyg. 2003 Jun; 68(6):671-7.
  55. Shi Y, Sawada J, Sui G, Affar el B, Whetstine JR, Lan F, Ogawa H, Luke MP, Nakatani Y, Shi Y. Coordinated histone modifications mediated by a CtBP co-repressor complex. Nature. 2003 Apr 17; 422(6933):735-8.
  56. Mayo MW, Denlinger CE, Broad RM, Yeung F, Reilly ET, Shi Y, Jones DR. Ineffectiveness of histone deacetylase inhibitors to induce apoptosis involves the transcriptional activation of NF-kappa B through the Akt pathway. J Biol Chem. 2003 May 23; 278(21):18980-9.
  57. Gay F, Calvo D, Lo MC, Ceron J, Maduro M, Lin R, Shi Y. Acetylation regulates subcellular localization of the Wnt signaling nuclear effector POP-1. Genes Dev. 2003 Mar 15; 17(6):717-22.
  58. Gaudilliere B, Shi Y, Bonni A. RNA interference reveals a requirement for myocyte enhancer factor 2A in activity-dependent neuronal survival. J Biol Chem. 2002 Nov 29; 277(48):46442-6.
  59. Shim EY, Walker AK, Shi Y, Blackwell TK. CDK-9/cyclin T (P-TEFb) is required in two postinitiation pathways for transcription in the C. elegans embryo. Genes Dev. 2002 Aug 15; 16(16):2135-46.
  60. Dufourcq P, Victor M, Gay F, Calvo D, Hodgkin J, Shi Y. Functional requirement for histone deacetylase 1 in Caenorhabditis elegans gonadogenesis. Mol Cell Biol. 2002 May; 22(9):3024-34.
  61. Sui G, Soohoo C, Affar el B, Gay F, Shi Y, Forrester WC, Shi Y. A DNA vector-based RNAi technology to suppress gene expression in mammalian cells. Proc Natl Acad Sci U S A. 2002 Apr 16; 99(8):5515-20.
  62. Victor M, Bei Y, Gay F, Calvo D, Mello C, Shi Y. HAT activity is essential for CBP-1-dependent transcription and differentiation in Caenorhabditis elegans. EMBO Rep. 2002 Jan; 3(1):50-5.
  63. Calvo D, Victor M, Gay F, Sui G, Luke MP, Dufourcq P, Wen G, Maduro M, Rothman J, Shi Y. A POP-1 repressor complex restricts inappropriate cell type-specific gene transcription during Caenorhabditis elegans embryogenesis. EMBO J. 2001 Dec 17; 20(24):7197-208.
  64. Walker AK, Rothman JH, Shi Y, Blackwell TK. Distinct requirements for C.elegans TAF(II)s in early embryonic transcription. EMBO J. 2001 Sep 17; 20(18):5269-79.
  65. Oei SL, Shi Y. Poly(ADP-ribosyl)ation of transcription factor Yin Yang 1 under conditions of DNA damage. Biochem Biophys Res Commun. 2001 Jul 6; 285(1):27-31.
  66. Oei SL, Shi Y. Transcription factor Yin Yang 1 stimulates poly(ADP-ribosyl)ation and DNA repair. Biochem Biophys Res Commun. 2001 Jun 8; 284(2):450-4.
  67. Coull JJ, Romerio F, Sun JM, Volker JL, Galvin KM, Davie JR, Shi Y, Hansen U, Margolis DM. The human factors YY1 and LSF repress the human immunodeficiency virus type 1 long terminal repeat via recruitment of histone deacetylase 1. J Virol. 2000 Aug; 74(15):6790-9.
  68. Walker AK, See R, Batchelder C, Kophengnavong T, Gronniger JT, Shi Y, Blackwell TK. A conserved transcription motif suggesting functional parallels between Caenorhabditis elegans SKN-1 and Cap'n'Collar-related basic leucine zipper proteins. J Biol Chem. 2000 Jul 21; 275(29):22166-71.
  69. Sze JY, Victor M, Loer C, Shi Y, Ruvkun G. Food and metabolic signalling defects in a Caenorhabditis elegans serotonin-synthesis mutant. Nature. 2000 Feb 3; 403(6769):560-4.
  70. Kato Y, Shi Y, He X. Neuralization of the Xenopus embryo by inhibition of p300/ CREB-binding protein function. J Neurosci. 1999 Nov 1; 19(21):9364-73.
  71. Donohoe ME, Zhang X, McGinnis L, Biggers J, Li E, Shi Y. Targeted disruption of mouse Yin Yang 1 transcription factor results in peri-implantation lethality. Mol Cell Biol. 1999 Oct; 19(10):7237-44.
  72. Johnstone RW, Tommerup N, Hansen C, Vissing H, Shi Y. Structural organization, tissue expression, and chromosomal localization of Ciao 1, a functional modulator of the Wilms' tumor suppressor, WT1. Immunogenetics. 1999 Sep; 49(10):900-5.
  73. Cook J, Krishnan S, Ananth S, Sells SF, Shi Y, Walther MM, Linehan WM, Sukhatme VP, Weinstein MH, Rangnekar VM. Decreased expression of the pro-apoptotic protein Par-4 in renal cell carcinoma. Oncogene. 1999 Feb 4; 18(5):1205-8.
  74. Johnstone RW, Tommerup N, Hansen C, Vissing H, Shi Y. Mapping of the human PAWR (par-4) gene to chromosome 12q21. Genomics. 1998 Oct 15; 53(2):241-3.
  75. Johnstone RW, Wang J, Tommerup N, Vissing H, Roberts T, Shi Y. Ciao 1 is a novel WD40 protein that interacts with the tumor suppressor protein WT1. J Biol Chem. 1998 May 1; 273(18):10880-7.
  76. Bauknecht T, Shi Y. Overexpression of C/EBPbeta represses human papillomavirus type 18 upstream regulatory region activity in HeLa cells by interfering with the binding of TATA-binding protein. J Virol. 1998 Mar; 72(3):2113-24.
  77. Galvin KM, Shi Y. Multiple mechanisms of transcriptional repression by YY1. Mol Cell Biol. 1997 Jul; 17(7):3723-32.
  78. Sells SF, Han SS, Muthukkumar S, Maddiwar N, Johnstone R, Boghaert E, Gillis D, Liu G, Nair P, Monnig S, Collini P, Mattson MP, Sukhatme VP, Zimmer SG, Wood DP, McRoberts JW, Shi Y, Rangnekar VM. Expression and function of the leucine zipper protein Par-4 in apoptosis. Mol Cell Biol. 1997 Jul; 17(7):3823-32.
  79. Gerritsen ME, Williams AJ, Neish AS, Moore S, Shi Y, Collins T. CREB-binding protein/p300 are transcriptional coactivators of p65. Proc Natl Acad Sci U S A. 1997 Apr 1; 94(7):2927-32.
  80. Li WW, Hsiung Y, Wong V, Galvin K, Zhou Y, Shi Y, Lee AS. Suppression of grp78 core promoter element-mediated stress induction by the dbpA and dbpB (YB-1) cold shock domain proteins. Mol Cell Biol. 1997 Jan; 17(1):61-8.
  81. Johnstone RW, See RH, Sells SF, Wang J, Muthukkumar S, Englert C, Haber DA, Licht JD, Sugrue SP, Roberts T, Rangnekar VM, Shi Y. A novel repressor, par-4, modulates transcription and growth suppression functions of the Wilms' tumor suppressor WT1. Mol Cell Biol. 1996 Dec; 16(12):6945-56.
  82. Bauknecht T, See RH, Shi Y. A novel C/EBP beta-YY1 complex controls the cell-type-specific activity of the human papillomavirus type 18 upstream regulatory region. J Virol. 1996 Nov; 70(11):7695-705.
  83. Lee JS, See RH, Deng T, Shi Y. Adenovirus E1A downregulates cJun- and JunB-mediated transcription by targeting their coactivator p300. Mol Cell Biol. 1996 Aug; 16(8):4312-26.
  84. Lee JS, Zhang X, Shi Y. Differential interactions of the CREB/ATF family of transcription factors with p300 and adenovirus E1A. J Biol Chem. 1996 Jul 26; 271(30):17666-74.
  85. Wang J, Auger KR, Jarvis L, Shi Y, Roberts TM. Direct association of Grb2 with the p85 subunit of phosphatidylinositol 3-kinase. J Biol Chem. 1995 May 26; 270(21):12774-80.
  86. Lee JS, Galvin KM, See RH, Eckner R, Livingston D, Moran E, Shi Y. Relief of YY1 transcriptional repression by adenovirus E1A is mediated by E1A-associated protein p300. Genes Dev. 1995 May 15; 9(10):1188-98.
  87. Reddy JC, Morris JC, Wang J, English MA, Haber DA, Shi Y, Licht JD. WT1-mediated transcriptional activation is inhibited by dominant negative mutant proteins. J Biol Chem. 1995 May 5; 270(18):10878-84.
  88. Lee JS, See RH, Galvin KM, Wang J, Shi Y. Functional interactions between YY1 and adenovirus E1A. Nucleic Acids Res. 1995 Mar 25; 23(6):925-31.
  89. Bauknecht T, Jundt F, Herr I, Oehler T, Delius H, Shi Y, Angel P, Zur Hausen H. A switch region determines the cell type-specific positive or negative action of YY1 on the activity of the human papillomavirus type 18 promoter. J Virol. 1995 Jan; 69(1):1-12.
  90. Mills LK, Shi Y, Millette RL. YY1 is the cellular factor shown previously to bind to regulatory regions of several leaky-late (beta gamma, gamma 1) genes of herpes simplex virus type 1. J Virol. 1994 Feb; 68(2):1234-8.
  91. Riggs KJ, Saleque S, Wong KK, Merrell KT, Lee JS, Shi Y, Calame K. Yin-yang 1 activates the c-myc promoter. Mol Cell Biol. 1993 Dec; 13(12):7487-95.
  92. Lee JS, Galvin KM, Shi Y. Evidence for physical interaction between the zinc-finger transcription factors YY1 and Sp1. Proc Natl Acad Sci U S A. 1993 Jul 1; 90(13):6145-9.
  93. Lee TC, Shi Y, Schwartz RJ. Displacement of BrdUrd-induced YY1 by serum response factor activates skeletal alpha-actin transcription in embryonic myoblasts. Proc Natl Acad Sci U S A. 1992 Oct 15; 89(20):9814-8.
  94. Seto E, Shi Y, Shenk T. YY1 is an initiator sequence-binding protein that directs and activates transcription in vitro. Nature. 1991 Nov 21; 354(6350):241-5.
  95. Shi Y, Seto E, Chang LS, Shenk T. Transcriptional repression by YY1, a human GLI-Krüppel-related protein, and relief of repression by adenovirus E1A protein. Cell. 1991 Oct 18; 67(2):377-88.
  96. Montalvo EA, Shi Y, Shenk TE, Levine AJ. Negative regulation of the BZLF1 promoter of Epstein-Barr virus. J Virol. 1991 Jul; 65(7):3647-55.
  97. Shi Y, Rodriguez M, Shahan K, Derman E. Subfamily of submaxillary gland-specific Mup genes: chromosomal linkage and sequence comparison with liver-specific Mup genes. Nucleic Acids Res. 1989 Aug 11; 17(15):6191-203.
  98. Chang LS, Shi Y, Shenk T. Adeno-associated virus P5 promoter contains an adenovirus E1A-inducible element and a binding site for the major late transcription factor. J Virol. 1989 Aug; 63(8):3479-88.
  99. Shi Y, Son HJ, Shahan K, Rodriguez M, Costantini F, Derman E. Silent genes in the mouse major urinary protein gene family. Proc Natl Acad Sci U S A. 1989 Jun; 86(12):4584-8.
  100. Shahan K, Denaro M, Gilmartin M, Shi Y, Derman E. Expression of six mouse major urinary protein genes in the mammary, parotid, sublingual, submaxillary, and lachrymal glands and in the liver. Mol Cell Biol. 1987 May; 7(5):1947-54.
  101. Sui G, Affar el B, Shi Y, Brignone C, Wall NR, Yin P, Donohoe M, Luke MP, Calvo D, Grossman SR, Shi Y. Yin Yang 1 is a negative regulator of p53. Cell. 2004 Jun 25; 117(7):859-72.
  102. Rafiee P, Shi Y, Kong X, Pritchard KA, Tweddell JS, Litwin SB, Mussatto K, Jaquiss RD, Su J, Baker JE. Activation of protein kinases in chronically hypoxic infant human and rabbit hearts: role in cardioprotection. Circulation. 2002 Jul 9; 106(2):239-45.
  103. Wu S, Shi Y, Mulligan P, Gay F, Landry J, Liu H, Lu J, Qi HH, Wang W, Nickoloff JA, Wu C, Shi Y. A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair. Nat Struct Mol Biol. 2007 Dec; 14(12):1165-72.
  104. Westbrook TF, Hu G, Ang XL, Mulligan P, Pavlova NN, Liang A, Leng Y, Maehr R, Shi Y, Harper JW, Elledge SJ. SCFbeta-TRCP controls oncogenic transformation and neural differentiation through REST degradation. Nature. 2008 Mar 20; 452(7185):370-4.
  105. Liu H, Schmidt-Supprian M, Shi Y, Hobeika E, Barteneva N, Jumaa H, Pelanda R, Reth M, Skok J, Rajewsky K, Shi Y. Yin Yang 1 is a critical regulator of B-cell development. Genes Dev. 2007 May 15; 21(10):1179-89.
  106. See RH, Calvo D, Shi Y, Kawa H, Luke MP, Yuan Z, Shi Y. Stimulation of p300-mediated transcription by the kinase MEKK1. J Biol Chem. 2001 May 11; 276(19):16310-7.
  107. Ongusaha PP, Qi HH, Raj L, Kim YB, Aaronson SA, Davis RJ, Shi Y, Liao JK, Lee SW. Identification of ROCK1 as an upstream activator of the JIP-3 to JNK signaling axis in response to UVB damage. Sci Signal. 2008 Nov 25; 1(47):ra14.
  108. Nasrin N, Ogg S, Cahill CM, Biggs W, Nui S, Dore J, Calvo D, Shi Y, Ruvkun G, Alexander-Bridges MC. DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells. Proc Natl Acad Sci U S A. 2000 Sep 12; 97(19):10412-7.
  109. Ding H, Schwarz DS, Keene A, Affar el B, Fenton L, Xia X, Shi Y, Zamore PD, Xu Z. Selective silencing by RNAi of a dominant allele that causes amyotrophic lateral sclerosis. Aging Cell. 2003 Aug; 2(4):209-17.
  110. Yuan ZM, Huang Y, Ishiko T, Nakada S, Utsugisawa T, Shioya H, Utsugisawa Y, Shi Y, Weichselbaum R, Kufe D. Function for p300 and not CBP in the apoptotic response to DNA damage. Oncogene. 1999 Oct 7; 18(41):5714-7.
  111. Qi HH, Sarkissian M, Hu GQ, Wang Z, Bhattacharjee A, Gordon DB, Gonzales M, Lan F, Ongusaha PP, Huarte M, Yaghi NK, Lim H, Garcia BA, Brizuela L, Zhao K, Roberts TM, Shi Y. Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development. Nature. 2010 Jul 22; 466(7305):503-7.
  112. Fang R, Barbera AJ, Xu Y, Rutenberg M, Leonor T, Bi Q, Lan F, Mei P, Yuan GC, Lian C, Peng J, Cheng D, Sui G, Kaiser UB, Shi Y, Shi YG. Human LSD2/KDM1b/AOF1 regulates gene transcription by modulating intragenic H3K4me2 methylation. Mol Cell. 2010 Jul 30; 39(2):222-33.
  113. Iwase S, Lan F, Bayliss P, de la Torre-Ubieta L, Huarte M, Qi HH, Whetstine JR, Bonni A, Roberts TM, Shi Y. The X-linked mental retardation gene SMCX/JARID1C defines a family of histone H3 lysine 4 demethylases. Cell. 2007 Mar 23; 128(6):1077-88.
  114. Nottke A, Colaiácovo MP, Shi Y. Developmental roles of the histone lysine demethylases. Development. 2009 Mar; 136(6):879-89.
  115. Dango S, Mosammaparast N, Sowa ME, Xiong LJ, Wu F, Park K, Rubin M, Gygi S, Harper JW, Shi Y. DNA unwinding by ASCC3 helicase is coupled to ALKBH3-dependent DNA alkylation repair and cancer cell proliferation. Mol Cell. 2011 Nov 4; 44(3):373-84.
  116. Lan F, Nottke AC, Shi Y. Mechanisms involved in the regulation of histone lysine demethylases. Curr Opin Cell Biol. 2008 Jun; 20(3):316-25.
  117. Shi Y. Mammalian RNAi for the masses. Trends Genet. 2003 Jan; 19(1):9-12.
  118. Kawasaki H, Song J, Eckner R, Ugai H, Chiu R, Taira K, Shi Y, Jones N, Yokoyama KK. p300 and ATF-2 are components of the DRF complex, which regulates retinoic acid- and E1A-mediated transcription of the c-jun gene in F9 cells. Genes Dev. 1998 Jan 15; 12(2):233-45.
  119. Yuan ZM, Huang Y, Ishiko T, Nakada S, Utsugisawa T, Shioya H, Utsugisawa Y, Yokoyama K, Weichselbaum R, Shi Y, Kufe D. Role for p300 in stabilization of p53 in the response to DNA damage. J Biol Chem. 1999 Jan 22; 274(4):1883-6.
  120. Horwitz AA, Affar el B, Heine GF, Shi Y, Parvin JD. A mechanism for transcriptional repression dependent on the BRCA1 E3 ubiquitin ligase. Proc Natl Acad Sci U S A. 2007 Apr 17; 104(16):6614-9.
  121. Xu Y, Wu F, Tan L, Kong L, Xiong L, Deng J, Barbera AJ, Zheng L, Zhang H, Huang S, Min J, Nicholson T, Chen T, Xu G, Shi Y, Zhang K, Shi YG. Genome-wide regulation of 5hmC, 5mC, and gene expression by Tet1 hydroxylase in mouse embryonic stem cells. Mol Cell. 2011 May 20; 42(4):451-64.
  122. Matthews AG, Kuo AJ, Ramón-Maiques S, Han S, Champagne KS, Ivanov D, Gallardo M, Carney D, Cheung P, Ciccone DN, Walter KL, Utz PJ, Shi Y, Kutateladze TG, Yang W, Gozani O, Oettinger MA. RAG2 PHD finger couples histone H3 lysine 4 trimethylation with V(D)J recombination. Nature. 2007 Dec 13; 450(7172):1106-10.
  123. Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y. Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression. Nature. 2007 Aug 9; 448(7154):718-22.
  124. Blättler SM, Cunningham JT, Verdeguer F, Chim H, Haas W, Liu H, Romanino K, Rüegg MA, Gygi SP, Shi Y, Puigserver P. Yin Yang 1 deficiency in skeletal muscle protects against rapamycin-induced diabetic-like symptoms through activation of insulin/IGF signaling. Cell Metab. 2012 Apr 4; 15(4):505-17.
  125. Qi HH, Ongusaha PP, Myllyharju J, Cheng D, Pakkanen O, Shi Y, Lee SW, Peng J, Shi Y. Prolyl 4-hydroxylation regulates Argonaute 2 stability. Nature. 2008 Sep 18; 455(7211):421-4.
  126. See RH, Shi Y. Adenovirus E1B 19,000-molecular-weight protein activates c-Jun N-terminal kinase and c-Jun-mediated transcription. Mol Cell Biol. 1998 Jul; 18(7):4012-22.
  127. Bates EA, Victor M, Jones AK, Shi Y, Hart AC. Differential contributions of Caenorhabditis elegans histone deacetylases to huntingtin polyglutamine toxicity. J Neurosci. 2006 Mar 8; 26(10):2830-8.
  128. Tan MK, Lim HJ, Bennett EJ, Shi Y, Harper JW. Parallel SCF adaptor capture proteomics reveals a role for SCFFBXL17 in NRF2 activation via BACH1 repressor turnover. Mol Cell. 2013 Oct 10; 52(1):9-24.
  129. Lim HJ, Dimova NV, Tan MK, Sigoillot FD, King RW, Shi Y. The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20. Mol Cell Biol. 2013 Nov; 33(21):4166-80.
  130. Alpatov R, Lesch BJ, Nakamoto-Kinoshita M, Blanco A, Chen S, Stützer A, Armache KJ, Simon MD, Xu C, Ali M, Murn J, Prisic S, Kutateladze TG, Vakoc CR, Min J, Kingston RE, Fischle W, Warren ST, Page DC, Shi Y. A chromatin-dependent role of the fragile X mental retardation protein FMRP in the DNA damage response. Cell. 2014 May 8; 157(4):869-81.
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