Bing Ren

InstitutionUniversity of California San Diego
DepartmentCellular and Molecular Medicine
Address9500 Gilman Drive #0653
La Jolla CA 92093
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    Collapse Overview 
    Collapse Overview
    Our laboratory is interested in understanding how the complex gene regulatory networks in mammalian cells control cellular proliferation and differentiation. The research is divided into two general areas: 1) the development of genomics and bioinformatics tools that allow genome wide identification of regulatory targets for transcription factors; and, 2) the application of these tools to the study of transcription factors that play critical roles in cancer.

    Research Focus Areas:

  • Genetics and Genomics

  • Gene Expression and Regulation

  • Signal Transduction

  • Collapse Research 
    Collapse Research Activities and Funding
    High throughput CRISPR-mediated functional validation of regulatory elements
    NIH/NHGRI UM1HG009402Feb 1, 2017 - Jan 31, 2021
    Role: Principal Investigator
    San Diego Center for 4D Nucleome Research
    NIH/NIDDK U54DK107977Sep 30, 2015 - Jul 31, 2020
    Role: Principal Investigator
    The Organizational Hub and Web Portal for the 4D Nucleome Network
    NIH/NCI U01CA200147Sep 1, 2015 - Aug 31, 2020
    Role: Principal Investigator
    Non-coding Variants Predisposing to Age-related Macular Degeneration
    NIH/NHGRI R01HG008135Aug 24, 2015 - Jun 30, 2018
    Role: Principal Investigator
    Functional Analysis of T2D Associated Non-coding SNPs
    NIH/NIDDK U01DK105541May 1, 2015 - Apr 30, 2020
    Role: Principal Investigator
    Integrative Analysis of Haplotype-Resolved Human Epigenome Maps
    NIH/NIEHS R01ES024984Sep 8, 2014 - Aug 31, 2017
    Role: Principal Investigator
    Center for Mammalian Regulatory Genomics
    NIH/NHGRI U54HG006997Sep 21, 2012 - Jul 31, 2017
    Role: Principal Investigator
    The San Diego Epigenome Center
    NIH/NIEHS U01ES017166Sep 29, 2008 - Jun 30, 2014
    Role: Principal Investigator
    Genome-wide map of active promoters in the mouse cells
    NIH/NHGRI R01HG003991Sep 18, 2008 - Jul 31, 2012
    Role: Principal Investigator
    NIH/NCI R33CA105829Aug 16, 2004 - Oct 31, 2008
    Role: Principal Investigator
    NIH/NCI R21CA105829Aug 16, 2004 - Jul 31, 2005
    Role: Principal Investigator
    Mapping transcriptional regulatory elements in human DNA
    NIH/NHGRI U01HG003151Sep 30, 2003 - Sep 30, 2008
    Role: Principal Investigator
    Graduate Training Program in Bioinformatics
    NIH/NIGMS T32GM008806Jul 1, 2001 - Jun 30, 2021
    Role: Principal Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Meng Z, Qiu Y, Lin KC, Kumar A, Placone JK, Fang C, Wang KC, Lu S, Pan M, Hong AW, Moroishi T, Luo M, Plouffe SW, Diao Y, Ye Z, Park HW, Wang X, Yu FX, Chien S, Wang CY, Ren B, Engler AJ, Guan KL. RAP2 mediates mechanoresponses of the Hippo pathway. Nature. 2018 Aug; 560(7720):655-660. PMID: 30135582.
      View in: PubMed
    2. Link VM, Duttke SH, Chun HB, Holtman IR, Westin E, Hoeksema MA, Abe Y, Skola D, Romanoski CE, Tao J, Fonseca GJ, Troutman TD, Spann NJ, Strid T, Sakai M, Yu M, Hu R, Fang R, Metzler D, Ren B, Glass CK. Analysis of Genetically Diverse Macrophages Reveals Local and Domain-wide Mechanisms that Control Transcription Factor Binding and Function. Cell. 2018 May 05. PMID: 29779944.
      View in: PubMed
    3. Fei J, Ishii H, Hoeksema MA, Meitinger F, Kassavetis GA, Glass CK, Ren B, Kadonaga JT. NDF, a nucleosome-destabilizing factor that facilitates transcription through nucleosomes. Genes Dev. 2018 May 01; 32(9-10):682-694. PMID: 29759984.
      View in: PubMed
    4. Koga T, Li B, Figueroa JM, Ren B, Chen CC, Carter BS, Furnari FB. Mapping of genomic EGFRvIII deletions in glioblastoma: insight into rearrangement mechanisms and biomarker development. Neuro Oncol. 2018 Apr 12. PMID: 29660021.
      View in: PubMed
    5. Lee J, Liao R, Wang G, Yang BH, Luo X, Varki NM, Qiu SJ, Ren B, Fu W, Feng GS. Preventive Inhibition of Liver Tumorigenesis by Systemic Activation of Innate Immune Functions. Cell Rep. 2017 Nov 14; 21(7):1870-1882. PMID: 29141219.
      View in: PubMed
    6. Rosa-Garrido M, Chapski DJ, Schmitt AD, Kimball TH, Karbassi E, Monte E, Balderas E, Pellegrini M, Shih TT, Soehalim E, Liem D, Ping P, Galjart NJ, Ren S, Wang Y, Ren B, Vondriska TM. High-Resolution Mapping of Chromatin Conformation in Cardiac Myocytes Reveals Structural Remodeling of the Epigenome in Heart Failure. Circulation. 2017 Oct 24; 136(17):1613-1625. PMID: 28802249.
      View in: PubMed
    7. Yu M, Ren B. The Three-Dimensional Organization of Mammalian Genomes. Annu Rev Cell Dev Biol. 2017 Oct 06; 33:265-289. PMID: 28783961.
      View in: PubMed
    8. DeBoever C, Li H, Jakubosky D, Benaglio P, Reyna J, Olson KM, Huang H, Biggs W, Sandoval E, D'Antonio M, Jepsen K, Matsui H, Arias A, Ren B, Nariai N, Smith EN, D'Antonio-Chronowska A, Farley EK, Frazer KA. Large-Scale Profiling Reveals the Influence of Genetic Variation on Gene Expression in Human Induced Pluripotent Stem Cells. Cell Stem Cell. 2017 04 06; 20(4):533-546.e7. PMID: 28388430.
      View in: PubMed
    9. Nechemia-Arbely Y, Fachinetti D, Miga KH, Sekulic N, Soni GV, Kim DH, Wong AK, Lee AY, Nguyen K, Dekker C, Ren B, Black BE, Cleveland DW. Human centromeric CENP-A chromatin is a homotypic, octameric nucleosome at all cell cycle points. J Cell Biol. 2017 03 06; 216(3):607-621. PMID: 28235947.
      View in: PubMed
    10. Turner KM, Deshpande V, Beyter D, Koga T, Rusert J, Lee C, Li B, Arden K, Ren B, Nathanson DA, Kornblum HI, Taylor MD, Kaushal S, Cavenee WK, Wechsler-Reya R, Furnari FB, Vandenberg SR, Rao PN, Wahl GM, Bafna V, Mischel PS. Extrachromosomal oncogene amplification drives tumour evolution and genetic heterogeneity. Nature. 2017 03 02; 543(7643):122-125. PMID: 28178237.
      View in: PubMed
    11. Schmitt AD, Hu M, Jung I, Xu Z, Qiu Y, Tan CL, Li Y, Lin S, Lin Y, Barr CL, Ren B. A Compendium of Chromatin Contact Maps Reveals Spatially Active Regions in the Human Genome. Cell Rep. 2016 11 15; 17(8):2042-2059. PMID: 27851967.
      View in: PubMed
    12. Schmitt AD, Hu M, Ren B. Genome-wide mapping and analysis of chromosome architecture. Nat Rev Mol Cell Biol. 2016 12; 17(12):743-755. PMID: 27580841.
      View in: PubMed
    13. Diao Y, Li B, Meng Z, Jung I, Lee AY, Dixon J, Maliskova L, Guan KL, Shen Y, Ren B. A new class of temporarily phenotypic enhancers identified by CRISPR/Cas9-mediated genetic screening. Genome Res. 2016 Mar; 26(3):397-405. PMID: 26813977; PMCID: PMC4772021.
    14. Ren B, Yue F. Transcriptional Enhancers: Bridging the Genome and Phenome. Cold Spring Harb Symp Quant Biol. 2015; 80:17-26. PMID: 26582789.
      View in: PubMed
    15. Huang X, Wang X, Lu SM, Chen C, Wang J, Zheng YY, Ren BH, Xu L. Clinicopathological and prognostic significance of MUC4 expression in cancers: evidence from meta-analysis. Int J Clin Exp Med. 2015; 8(7):10274-83. PMID: 26379819; PMCID: PMC4565202.
    16. Schultz MD, He Y, Whitaker JW, Hariharan M, Mukamel EA, Leung D, Rajagopal N, Nery JR, Urich MA, Chen H, Lin S, Lin Y, Jung I, Schmitt AD, Selvaraj S, Ren B, Sejnowski TJ, Wang W, Ecker JR. Human body epigenome maps reveal noncanonical DNA methylation variation. Nature. 2015 Jul 09; 523(7559):212-6. PMID: 26030523; PMCID: PMC4499021.
    17. Ren B, Dixon JR. A CRISPR Connection between Chromatin Topology and Genetic Disorders. Cell. 2015 May 21; 161(5):955-957. PMID: 26000472; PMCID: PMC4478077.
    18. Wang A, Yue F, Li Y, Xie R, Harper T, Patel NA, Muth K, Palmer J, Qiu Y, Wang J, Lam DK, Raum JC, Stoffers DA, Ren B, Sander M. Epigenetic priming of enhancers predicts developmental competence of hESC-derived endodermal lineage intermediates. Cell Stem Cell. 2015 Apr 02; 16(4):386-99. PMID: 25842977; PMCID: PMC4478079.
    19. Dixon JR, Jung I, Selvaraj S, Shen Y, Antosiewicz-Bourget JE, Lee AY, Ye Z, Kim A, Rajagopal N, Xie W, Diao Y, Liang J, Zhao H, Lobanenkov VV, Ecker JR, Thomson JA, Ren B. Chromatin architecture reorganization during stem cell differentiation. Nature. 2015 Feb 19; 518(7539):331-6. PMID: 25693564; PMCID: PMC4515363.
    20. Yue F, Cheng Y, Breschi A, Vierstra J, Wu W, Ryba T, Sandstrom R, Ma Z, Davis C, Pope BD, Shen Y, Pervouchine DD, Djebali S, Thurman RE, Kaul R, Rynes E, Kirilusha A, Marinov GK, Williams BA, Trout D, Amrhein H, Fisher-Aylor K, Antoshechkin I, DeSalvo G, See LH, Fastuca M, Drenkow J, Zaleski C, Dobin A, Prieto P, Lagarde J, Bussotti G, Tanzer A, Denas O, Li K, Bender MA, Zhang M, Byron R, Groudine MT, McCleary D, Pham L, Ye Z, Kuan S, Edsall L, Wu YC, Rasmussen MD, Bansal MS, Kellis M, Keller CA, Morrissey CS, Mishra T, Jain D, Dogan N, Harris RS, Cayting P, Kawli T, Boyle AP, Euskirchen G, Kundaje A, Lin S, Lin Y, Jansen C, Malladi VS, Cline MS, Erickson DT, Kirkup VM, Learned K, Sloan CA, Rosenbloom KR, Lacerda de Sousa B, Beal K, Pignatelli M, Flicek P, Lian J, Kahveci T, Lee D, Kent WJ, Ramalho Santos M, Herrero J, Notredame C, Johnson A, Vong S, Lee K, Bates D, Neri F, Diegel M, Canfield T, Sabo PJ, Wilken MS, Reh TA, Giste E, Shafer A, Kutyavin T, Haugen E, Dunn D, Reynolds AP, Neph S, Humbert R, Hansen RS, De Bruijn M, Selleri L, Rudensky A, Josefowicz S, Samstein R, Eichler EE, Orkin SH, Levasseur D, Papayannopoulou T, Chang KH, Skoultchi A, Gosh S, Disteche C, Treuting P, Wang Y, Weiss MJ, Blobel GA, Cao X, Zhong S, Wang T, Good PJ, Lowdon RF, Adams LB, Zhou XQ, Pazin MJ, Feingold EA, Wold B, Taylor J, Mortazavi A, Weissman SM, Stamatoyannopoulos JA, Snyder MP, Guigo R, Gingeras TR, Gilbert DM, Hardison RC, Beer MA, Ren B. A comparative encyclopedia of DNA elements in the mouse genome. Nature. 2014 Nov 20; 515(7527):355-64. PMID: 25409824.
      View in: PubMed
    21. Ren BB, Yu Zh, Wang YL, Xu B. [Regulatory effect of electroacupuncture on heart and stomach of rats]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2014 Oct; 34(10):1212-5. PMID: 25509264.
      View in: PubMed
    22. Rajagopal N, Ernst J, Ray P, Wu J, Zhang M, Kellis M, Ren B. Distinct and predictive histone lysine acetylation patterns at promoters, enhancers, and gene bodies. G3 (Bethesda). 2014 Aug 12; 4(11):2051-63. PMID: 25122670; PMCID: PMC4232531.
    23. Gorkin DU, Leung D, Ren B. The 3D genome in transcriptional regulation and pluripotency. Cell Stem Cell. 2014 Jun 05; 14(6):762-75. PMID: 24905166; PMCID: PMC4107214.
    24. Leung D, Du T, Wagner U, Xie W, Lee AY, Goyal P, Li Y, Szulwach KE, Jin P, Lorincz MC, Ren B. Regulation of DNA methylation turnover at LTR retrotransposons and imprinted loci by the histone methyltransferase Setdb1. Proc Natl Acad Sci U S A. 2014 May 06; 111(18):6690-5. PMID: 24757056; PMCID: PMC4020067.
    25. Selvaraj S, R Dixon J, Bansal V, Ren B. Whole-genome haplotype reconstruction using proximity-ligation and shotgun sequencing. Nat Biotechnol. 2013 Dec; 31(12):1111-8. PMID: 24185094; PMCID: PMC4180835.
    26. Wang T, Liu J, Shen L, Tonti-Filippini J, Zhu Y, Jia H, Lister R, Whitaker JW, Ecker JR, Millar AH, Ren B, Wang W. STAR: an integrated solution to management and visualization of sequencing data. Bioinformatics. 2013 Dec 15; 29(24):3204-10. PMID: 24078702; PMCID: PMC3842760.
    27. Rivera CM, Ren B. Mapping human epigenomes. Cell. 2013 Sep 26; 155(1):39-55. PMID: 24074860; PMCID: PMC3838898.
    28. Xie W, Ren B. Developmental biology. Enhancing pluripotency and lineage specification. Science. 2013 Jul 19; 341(6143):245-7. PMID: 23869010.
      View in: PubMed
    29. Rajagopal N, Xie W, Li Y, Wagner U, Wang W, Stamatoyannopoulos J, Ernst J, Kellis M, Ren B. RFECS: a random-forest based algorithm for enhancer identification from chromatin state. PLoS Comput Biol. 2013; 9(3):e1002968. PMID: 23526891; PMCID: PMC3597546.
    30. Won KJ, Zhang X, Wang T, Ding B, Raha D, Snyder M, Ren B, Wang W. Comparative annotation of functional regions in the human genome using epigenomic data. Nucleic Acids Res. 2013 Apr; 41(8):4423-32. PMID: 23482391; PMCID: PMC3632130.
    31. Ren BB, Liu ZC, Xu B. [Observation on the efficacy of female obesity complicated with climacteric syndrome treated by acupuncture and moxibustion]. Zhongguo Zhen Jiu. 2012 Oct; 32(10):871-6. PMID: 23259259.
      View in: PubMed
    32. Ren BB, Yu Z, Xu B. [Overview of the two-way regulatory effect of acupuncture on gastrointestinal motility]. Zhongguo Zhen Jiu. 2012 Aug; 32(8):765-8. PMID: 23072106.
      View in: PubMed
    33. Lo MC, Peterson LF, Yan M, Cong X, Jin F, Shia WJ, Matsuura S, Ahn EY, Komeno Y, Ly M, Ommen HB, Chen IM, Hokland P, Willman CL, Ren B, Zhang DE. Combined gene expression and DNA occupancy profiling identifies potential therapeutic targets of t(8;21) AML. Blood. 2012 Aug 16; 120(7):1473-84. PMID: 22740448; PMCID: PMC3423785.
    34. Jin F, Li Y, Ren B, Natarajan R. Enhancers: multi-dimensional signal integrators. Transcription. 2011 Sep-Oct; 2(5):226-30. PMID: 22231119; PMCID: PMC3265780.
    35. Hawkins RD, Hon GC, Yang C, Antosiewicz-Bourget JE, Lee LK, Ngo QM, Klugman S, Ching KA, Edsall LE, Ye Z, Kuan S, Yu P, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Ren B. Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency. Cell Res. 2011 Oct; 21(10):1393-409. PMID: 21876557; PMCID: PMC3193447.
    36. Jin F, Li Y, Ren B, Natarajan R. PU.1 and C/EBP(alpha) synergistically program distinct response to NF-kappaB activation through establishing monocyte specific enhancers. Proc Natl Acad Sci U S A. 2011 Mar 29; 108(13):5290-5. PMID: 21402921; PMCID: PMC3069155.
    37. Harismendy O, Notani D, Song X, Rahim NG, Tanasa B, Heintzman N, Ren B, Fu XD, Topol EJ, Rosenfeld MG, Frazer KA. 9p21 DNA variants associated with coronary artery disease impair interferon-? signalling response. Nature. 2011 Feb 10; 470(7333):264-8. PMID: 21307941; PMCID: PMC3079517.
    38. Hawkins RD, Hon GC, Ren B. Next-generation genomics: an integrative approach. Nat Rev Genet. 2010 Jul; 11(7):476-86. PMID: 20531367; PMCID: PMC3321268.
    39. Won KJ, Ren B, Wang W. Genome-wide prediction of transcription factor binding sites using an integrated model. Genome Biol. 2010 Jan 22; 11(1):R7. PMID: 20096096; PMCID: PMC2847719.
    40. Hon G, Wang W, Ren B. Discovery and annotation of functional chromatin signatures in the human genome. PLoS Comput Biol. 2009 Nov; 5(11):e1000566. PMID: 19918365; PMCID: PMC2775352.
    41. Heintzman ND, Ren B. Finding distal regulatory elements in the human genome. Curr Opin Genet Dev. 2009 Dec; 19(6):541-9. PMID: 19854636; PMCID: PMC3321269.
    42. Hon GC, Hawkins RD, Ren B. Predictive chromatin signatures in the mammalian genome. Hum Mol Genet. 2009 Oct 15; 18(R2):R195-201. PMID: 19808796; PMCID: PMC2912651.
    43. Won KJ, Agarwal S, Shen L, Shoemaker R, Ren B, Wang W. An integrated approach to identifying cis-regulatory modules in the human genome. PLoS One. 2009; 4(5):e5501. PMID: 19434238; PMCID: PMC2677454.
    44. Heintzman ND, Hon GC, Hawkins RD, Kheradpour P, Stark A, Harp LF, Ye Z, Lee LK, Stuart RK, Ching CW, Ching KA, Antosiewicz-Bourget JE, Liu H, Zhang X, Green RD, Lobanenkov VV, Stewart R, Thomson JA, Crawford GE, Kellis M, Ren B. Histone modifications at human enhancers reflect global cell-type-specific gene expression. Nature. 2009 May 07; 459(7243):108-12. PMID: 19295514; PMCID: PMC2910248.
    45. Won KJ, Chepelev I, Ren B, Wang W. Prediction of regulatory elements in mammalian genomes using chromatin signatures. BMC Bioinformatics. 2008 Dec 18; 9:547. PMID: 19094206; PMCID: PMC2657164.
    46. Hon G, Ren B, Wang W. ChromaSig: a probabilistic approach to finding common chromatin signatures in the human genome. PLoS Comput Biol. 2008 Oct; 4(10):e1000201. PMID: 18927605; PMCID: PMC2556089.
    47. Maynard ND, Chen J, Stuart RK, Fan JB, Ren B. Genome-wide mapping of allele-specific protein-DNA interactions in human cells. Nat Methods. 2008 Apr; 5(4):307-9. PMID: 18345007.
      View in: PubMed
    48. Barrera LO, Li Z, Smith AD, Arden KC, Cavenee WK, Zhang MQ, Green RD, Ren B. Genome-wide mapping and analysis of active promoters in mouse embryonic stem cells and adult organs. Genome Res. 2008 Jan; 18(1):46-59. PMID: 18042645; PMCID: PMC2134779.
    49. Li D, Ren BH, Shen Y, Wu H, Wang C, Zhang L, Zhu J, Jing H. A Swine model for long-term evaluation of prosthetic heart valves. ANZ J Surg. 2007 Aug; 77(8):654-8. PMID: 17635278.
      View in: PubMed
    50. Kim TH, Abdullaev ZK, Smith AD, Ching KA, Loukinov DI, Green RD, Zhang MQ, Lobanenkov VV, Ren B. Analysis of the vertebrate insulator protein CTCF-binding sites in the human genome. Cell. 2007 Mar 23; 128(6):1231-45. PMID: 17382889; PMCID: PMC2572726.
    51. Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Van Calcar S, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B. Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome. Nat Genet. 2007 Mar; 39(3):311-8. PMID: 17277777.
      View in: PubMed
    52. Toyo-oka K, Bowen TJ, Hirotsune S, Li Z, Jain S, Ota S, Escoubet-Lozach L, Lozach LE, Garcia-Bassets I, Bassett IG, Lozach J, Rosenfeld MG, Glass CK, Eisenman R, Ren B, Hurlin P, Wynshaw-Boris A. Mnt-deficient mammary glands exhibit impaired involution and tumors with characteristics of myc overexpression. Cancer Res. 2006 Jun 01; 66(11):5565-73. PMID: 16740691.
      View in: PubMed
    53. Barrera LO, Ren B. The transcriptional regulatory code of eukaryotic cells--insights from genome-wide analysis of chromatin organization and transcription factor binding. Curr Opin Cell Biol. 2006 Jun; 18(3):291-8. PMID: 16647254.
      View in: PubMed
    54. Hawkins RD, Ren B. Genome-wide location analysis: insights on transcriptional regulation. Hum Mol Genet. 2006 Apr 15; 15 Spec No 1:R1-7. PMID: 16651365.
      View in: PubMed
    55. Kim TH, Ren B. Genome-wide analysis of protein-DNA interactions. Annu Rev Genomics Hum Genet. 2006; 7:81-102. PMID: 16722805.
      View in: PubMed
    56. Kim TH, Ren B. An all-round view of eukaryotic transcription. Genome Biol. 2006; 7(7):323. PMID: 16879733; PMCID: PMC1779551.
    57. Kim TH, Barrera LO, Zheng M, Qu C, Singer MA, Richmond TA, Wu Y, Green RD, Ren B. A high-resolution map of active promoters in the human genome. Nature. 2005 Aug 11; 436(7052):876-80. PMID: 15988478; PMCID: PMC1895599.
    58. Kim TH, Barrera LO, Qu C, Van Calcar S, Trinklein ND, Cooper SJ, Luna RM, Glass CK, Rosenfeld MG, Myers RM, Ren B. Direct isolation and identification of promoters in the human genome. Genome Res. 2005 Jun; 15(6):830-9. PMID: 15899964; PMCID: PMC1142473.
    59. Kim TH, Xiong H, Zhang Z, Ren B. beta-Catenin activates the growth factor endothelin-1 in colon cancer cells. Oncogene. 2005 Jan 20; 24(4):597-604. PMID: 15558022.
      View in: PubMed
    60. Ren B, Dynlacht BD. Use of chromatin immunoprecipitation assays in genome-wide location analysis of mammalian transcription factors. Methods Enzymol. 2004; 376:304-15. PMID: 14975314.
      View in: PubMed
    61. Li Z, Van Calcar S, Qu C, Cavenee WK, Zhang MQ, Ren B. A global transcriptional regulatory role for c-Myc in Burkitt's lymphoma cells. Proc Natl Acad Sci U S A. 2003 Jul 08; 100(14):8164-9. PMID: 12808131; PMCID: PMC166200.