1932

Abstract

In this perspective I look back on the twists and turns that influenced the direction of my scientific career over the past 40 years. From my early ambition to be a chemist to my training in Philadelphia and Bethesda as a molecular biologist, I benefited enormously from generous and valuable mentoring. In my independent career in Philadelphia and Princeton, I was motivated by a keen interest in the changes in gene expression that direct the development of the mammalian embryo and inspired by the creativity and energy of my students, fellows, and research staff. After twelve years as President of Princeton University, I have happily returned to the faculty of the Department of Molecular Biology.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-cellbio-100913-013512
2014-10-06
2024-06-16
Loading full text...

Full text loading...

/deliver/fulltext/cellbio/30/1/annurev-cellbio-100913-013512.html?itemId=/content/journals/10.1146/annurev-cellbio-100913-013512&mimeType=html&fmt=ahah

Literature Cited

  1. Alexander F, Young PR, Tilghman SM. 1984. Evolution of the albumin: α-fetoprotein ancestral gene from the amplification of a 27 nucleotide sequence. J. Mol. Biol. 173:159–73 [Google Scholar]
  2. Barlow DP, Stoger R, Herrmann BG, Saito K, Schweifer N. 1991. The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus. Nature 349:84–87 [Google Scholar]
  3. Bartolomei MS, Webber AL, Brunkow ME, Tilghman SM. 1993. Epigenetic mechanisms underlying the imprinting of the mouse H19 gene. Genes Dev. 7:1663–73 [Google Scholar]
  4. Bartolomei MS, Zemel S, Tilghman SM. 1991. Parental imprinting of the mouse H19 gene. Nature 351:153–55 [Google Scholar]
  5. Belayew A, Tilghman SM. 1982. Genetic analysis of α-fetoprotein synthesis in mice. Mol. Cell. Biol. 2:1427–35 [Google Scholar]
  6. Bell AC, Felsenfeld G. 2000. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature 405:482–85 [Google Scholar]
  7. Bell AC, West AG, Felsenfeld G. 1999. The protein CTCF is required for the enhancer blocking activity of vertebrate insulators. Cell 98:387–96 [Google Scholar]
  8. Berg P, Baltimore D, Brenner S, Roblin RO, Singer MF. 1975. Summary statement of the Asilomar conference on recombinant DNA molecules. Proc. Natl. Acad. Sci. USA 721981–84 [Google Scholar]
  9. Berget SM, Sharp PA. 1977. A spliced sequence at the 5′-terminus of adenovirus late mRNA. Brookhaven Symp. Biol. 29:332–44 [Google Scholar]
  10. Brannan CI, Dees EC, Ingram RS, Tilghman SM. 1990. The product of the H19 gene may function as an RNA. Mol. Cell. Biol. 10:28–36 [Google Scholar]
  11. Brinster RL, Chen HY, Trumbauer M, Senear AW, Warren R, Palmiter RD. 1981a. Somatic expression of herpes thymidine kinase in mice following injection of a fusion gene into eggs. Cell 27:223–31 [Google Scholar]
  12. Brinster RL, Chen HY, Trumbauer ME. 1981b. Mouse oocytes transcribe injected Xenopus 5S RNA gene. Science 211:396–98 [Google Scholar]
  13. Broker TR, Chow LT, Dunn AR, Gelinas RE, Hassell JA. et al. 1978. Adenovirus-2 messengers—an example of Baroque molecular architecture. Cold Spring Harb. Symp. Quant. Biol. 42:Pt. 1531–53 [Google Scholar]
  14. Brown JR. 1976. Structural origins of mammalian albumin. Fed. Proc. 35:2141–44 [Google Scholar]
  15. Brunkow ME, Tilghman SM. 1991. Ectopic expression of the H19 gene in mice causes prenatal lethality. Genes Dev. 5:1092–101 [Google Scholar]
  16. Burke DT, Rossi JM, Leung J, Koos DS, Tilghman SM. 1991. A mouse genomic library of yeast artificial chromosome clones. Mamm. Genome 1:65 [Google Scholar]
  17. Bush GL, Case SM, Wilson AC, Patton JL. 1977. Rapid speciation and chromosomal evolution in mammals. Proc. Natl. Acad. Sci. USA 74:3942–46 [Google Scholar]
  18. Cai X, Cullen BR. 2007. The imprinted H19 noncoding RNA is a primary microRNA precursor. RNA 13:313–16 [Google Scholar]
  19. Camper SA, Tilghman SM. 1989. Postnatal repression of the α-fetoprotein gene is enhancer independent. Genes Dev. 3:537–46 [Google Scholar]
  20. Carr MS, Getek KA, Levorse JM, Schmidt JV. 2006. Expression of a modified H19 RNA does not cause embryonic lethality in mice. Mamm. Genome 17:5–13 [Google Scholar]
  21. Chess A, Simon I, Cedar H, Axel R. 1994. Allelic inactivation regulates olfactory receptor gene expression. Cell 78:823–34 [Google Scholar]
  22. Curtis PJ, Weissmann C. 1976. Purification of globin messenger RNA from dimethylsulfoxide-induced Friend cells and detection of a putative globin messenger RNA precursor. J. Mol. Biol. 106:1067–75 [Google Scholar]
  23. Dawson WD. 1965. Fertility and size inheritance in a Peromyscus species cross. Evolution 19:44–55 [Google Scholar]
  24. DeChiara TM, Robertson EJ, Efstratiadis A. 1991. Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849–59 [Google Scholar]
  25. Eiferman FA, Young PR, Scott RW, Tilghman SM. 1981. Intragenic amplification and divergence in the mouse α-fetoprotein gene. Nature 294:713–18 [Google Scholar]
  26. Gabory A, Jammes H, Dandolo L. 2010. The H19 locus: role of an imprinted non-coding RNA in growth and development. BioEssays 32:473–80 [Google Scholar]
  27. Godbout R, Ingram R, Tilghman SM. 1986. Multiple regulatory elements in the intergenic region between the α-fetoprotein and albumin genes. Mol. Cell. Biol. 6:477–87 [Google Scholar]
  28. Godbout R, Ingram RS, Tilghman SM. 1988. Fine-structure mapping of the three mouse α-fetoprotein gene enhancers. Mol. Cell. Biol. 8:1169–78 [Google Scholar]
  29. Gorin MB, Cooper DL, Eiferman F, van de Rijn P, Tilghman SM. 1981. The evolution of α-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian α-fetoprotein and albumin. J. Biol. Chem. 256:1954–59 [Google Scholar]
  30. Gorin MB, Tilghman SM. 1980. Structure of the α-fetoprotein gene in the mouse. Proc. Natl. Acad. Sci. USA 77:1351–55 [Google Scholar]
  31. Hammer RE, Krumlauf R, Camper SA, Brinster RL, Tilghman SM. 1987. Diversity of α-fetoprotein gene expression in mice is generated by a combination of separate enhancer elements. Science 235:53–58 [Google Scholar]
  32. Hao Y, Crenshaw T, Moulton T, Newcomb E, Tycko B. 1993. Tumour-suppressor activity of H19 RNA. Nature 365:764–67 [Google Scholar]
  33. Hardies SC, Wells RD. 1976. Preparative fractionation of DNA restriction fragments by reversed phase column chromatography. Proc. Natl. Acad. Sci. USA 73:3117–21 [Google Scholar]
  34. Hark AT, Schoenherr CJ, Katz DJ, Ingram RS, Levorse JM, Tilghman SM. 2000. CTCF mediates methylation-sensitive enhancer-blocking activity at the H19/Igf2 locus. Nature 405:486–89 [Google Scholar]
  35. Hosoda K, Hammer RE, Richardson JA, Baynash AG, Cheung JC. et al. 1994. Targeted and natural (piebald-lethal) mutations of endothelin-B receptor gene produce megacolon associated with spotted coat color in mice. Cell 79:1267–76 [Google Scholar]
  36. Ingram RS, Scott RW, Tilghman SM. 1981. α-Fetoprotein and albumin genes are in tandem in the mouse genome. Proc. Natl. Acad. Sci. USA 78:4694–98 [Google Scholar]
  37. Jones BK, Levorse JM, Tilghman SM. 1998. Igf2 imprinting does not require its own DNA methylation or H19 RNA. Genes Dev. 12:2200–7 [Google Scholar]
  38. Keniry A, Oxley D, Monnier P, Kyba M, Dandolo L. et al. 2012. The H19 lincRNA is a developmental reservoir of miR-675 that suppresses growth and Igf1r. Nat. Cell Biol. 14:659–65 [Google Scholar]
  39. Kioussis D, Eiferman F, van de Rijn P, Gorin MB, Ingram RS, Tilghman SM. 1981. The evolution of α-fetoprotein and albumin. II. The structures of the α-fetoprotein and albumin genes in the mouse. J. Biol. Chem. 256:1960–67 [Google Scholar]
  40. Kioussis D, Reshef L, Cohen H, Tilghman SM, Iynedjian PB. et al. 1978. Alterations in translatable messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP) in rat liver cytosol during deinduction. J. Biol. Chem. 253:4327–32 [Google Scholar]
  41. Krumlauf R, Hammer RE, Tilghman SM, Brinster RL. 1985. Developmental regulation of α-fetoprotein genes in transgenic mice. Mol. Cell. Biol. 5:1639–48 [Google Scholar]
  42. Leder P, Tiemeier D, Enquist L. 1977. EK2 derivatives of bacteriophage lambda useful in the cloning of DNA from higher organisms: the lambdagtWES system. Science 196:175–77 [Google Scholar]
  43. Leighton PA, Ingram RS, Eggenschwiler J, Efstratiadis A, Tilghman SM. 1995a. Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature 375:34–39 [Google Scholar]
  44. Leighton PA, Saam JR, Ingram RS, Stewart CL, Tilghman SM. 1995b. An enhancer deletion affects both H19 and Igf2 expression. Genes Dev. 9:2079–89 [Google Scholar]
  45. Martin GR, Evans MJ. 1975. Differentiation of clonal lines of teratocarcinoma cells: formation of embryoid bodies in vitro. Proc. Natl. Acad. Sci. USA 72:1441–45 [Google Scholar]
  46. Matouk IJ, DeGroot N, Mezan S, Ayesh S, Abu-lail R. et al. 2007. The H19 non-coding RNA is essential for human tumor growth. PLOS ONE 2:e845 [Google Scholar]
  47. Meselson M, Stahl FW. 1958. The replication of DNA in Escherichia coli. Proc. Natl. Acad. Sci. USA 44:671–82 [Google Scholar]
  48. Metallinos DL, Oppenheimer AJ, Rinchik EM, Russell LB, Dietrich W, Tilghman SM. 1994. Fine structure mapping and deletion analysis of the murine piebald locus. Genetics 136:217–23 [Google Scholar]
  49. Moore T, Haig D. 1991. Genomic imprinting in mammalian development: a parental tug-of-war. Trends Genet. 7:45–49 [Google Scholar]
  50. Olsson M, Lindahl G, Ruoslahti E. 1977. Genetic control of alpha-fetoprotein synthesis in the mouse. J. Exp. Med. 145:819–27 [Google Scholar]
  51. Pachnis V, Belayew A, Tilghman SM. 1984. Locus unlinked to α-fetoprotein under the control of the murine raf and Rif genes. Proc. Natl. Acad. Sci. USA 81:5523–27 [Google Scholar]
  52. Perry WL 3rd, Vasicek TJ, Lee JJ, Rossi JM, Zeng L. et al. 1995. Phenotypic and molecular analysis of a transgenic insertional allele of the mouse Fused locus. Genetics 141:321–32 [Google Scholar]
  53. Ross J. 1976. A precursor of globin messenger RNA. J. Mol. Biol. 106:403–20 [Google Scholar]
  54. Rossi JM, Burke DT, Leung JC, Koos DS, Chen H, Tilghman SM. 1992. Genomic analysis using a yeast artificial chromosome library with mouse DNA inserts. Proc. Natl. Acad. Sci. USA 89:2456–60 [Google Scholar]
  55. Rossi JM, Chen H, Tilghman SM. 1994. Genetic map of the fused locus on mouse chromosome 17. Genomics 23:178–84 [Google Scholar]
  56. Schmidt JV, Levorse JM, Tilghman SM. 1999. Enhancer competition between H19 and Igf2 does not mediate their imprinting. Proc. Natl. Acad. Sci. USA 96:9733–38 [Google Scholar]
  57. Schoenherr CJ, Levorse JM, Tilghman SM. 2003. CTCF maintains differential methylation at the Igf2/H19 locus. Nat. Genet. 33:66–69 [Google Scholar]
  58. Scott RW, Vogt TF, Croke ME, Tilghman SM. 1984. Tissue-specific activation of a cloned α-fetoprotein gene during differentiation of a transfected embryonal carcinoma cell line. Nature 310:562–67 [Google Scholar]
  59. Shin MK, Levorse JM, Ingram RS, Tilghman SM. 1999. The temporal requirement for endothelin receptor-B signalling during neural crest development. Nature 402:496–501 [Google Scholar]
  60. Thomas M, White RL, Davis RW. 1976. Hybridization of RNA to double-stranded DNA: formation of R-loops. Proc. Natl. Acad. Sci. USA 73:2294–98 [Google Scholar]
  61. Tilghman SM, Curtis PJ, Tiemeier DC, Leder P, Weissmann C. 1978a. The intervening sequence of a mouse β-globin gene is transcribed within the 15S β-globin mRNA precursor. Proc. Natl. Acad. Sci. USA 75:1309–13 [Google Scholar]
  62. Tilghman SM, Hanson RW, Reshef L, Hopgood MF, Ballard FJ. 1974. Rapid loss of translatable messenger RNA of phosphoenolpyruvate carboxykinase during glucose repression in liver. Proc. Natl. Acad. Sci. USA 71:1304–8 [Google Scholar]
  63. Tilghman SM, Tiemeier DC, Polsky F, Edgell MH, Seidman JG. et al. 1977. Cloning specific segments of the mammalian genome: bacteriophage λ containing mouse globin and surrounding gene sequences. Proc. Natl. Acad. Sci. USA 74:4406–10 [Google Scholar]
  64. Tilghman SM, Tiemeier DC, Seidman JG, Peterlin BM, Sullivan M. et al. 1978b. Intervening sequence of DNA identified in the structural portion of a mouse β-globin gene. Proc. Natl. Acad. Sci. USA 75:725–29 [Google Scholar]
  65. Tremblay KD, Saam JR, Ingram RS, Tilghman SM, Bartolomei MS. 1995. A paternal-specific methylation imprint marks the alleles of the mouse H19 gene. Nat. Genet. 9:407–13 [Google Scholar]
  66. Vacher J, Camper SA, Krumlauf R, Compton RS, Tilghman SM. 1992. raf regulates the postnatal repression of the mouse α-fetoprotein gene at the posttranscriptional level. Mol. Cell. Biol. 12:856–64 [Google Scholar]
  67. van Raamsdonk CD, Tilghman SM. 2000. Dosage requirement and allelic expression of PAX6 during lens placode formation. Development 127:5439–48 [Google Scholar]
  68. Vrana PB, Fossella JA, Matteson P, del Rio T, O'Neill MJ, Tilghman SM. 2000. Genetic and epigenetic incompatibilities underlie hybrid dysgenesis in Peromyscus. Nat. Genet. 25:120–24 [Google Scholar]
  69. Vrana PB, Guan XJ, Ingram RS, Tilghman SM. 1998. Genomic imprinting is disrupted in interspecific Peromyscus hybrids. Nat. Genet. 20:362–65 [Google Scholar]
  70. Wilkins JF, Haig D. 2003. What good is genomic imprinting: the function of parent-specific gene expression. Nat. Rev. Genet. 4:359–68 [Google Scholar]
  71. Wolfe S, Bassett RN, Caldwell SM, Wasson FI. 1966. Reversal of the anhydropenicillin rearrangement. J. Am. Chem. Soc. 91:7205 [Google Scholar]
  72. Yoo-Warren H, Pachnis V, Ingram RS, Tilghman SM. 1988. Two regulatory domains flank the mouse H19 gene. Mol. Cell. Biol. 8:4707–15 [Google Scholar]
  73. Yoshimizu T, Miroglio A, Ripoche MA, Gabory A, Vernucci M. et al. 2008. The H19 locus acts in vivo as a tumor suppressor. Proc. Natl. Acad. Sci. USA 105:12417–22 [Google Scholar]
  74. Zemel S, Bartolomei MS, Tilghman SM. 1992. Physical linkage of two mammalian imprinted genes, H19 and insulin-like growth factor 2. Nat. Genet. 2:61–65 [Google Scholar]
  75. Zeng L, Fagotto F, Zhang T, Hsu W, Vasicek TJ. et al. 1997. The mouse Fused locus encodes Axin, an inhibitor of the Wnt signaling pathway that regulates embryonic axis formation. Cell 90:181–92 [Google Scholar]
/content/journals/10.1146/annurev-cellbio-100913-013512
Loading
/content/journals/10.1146/annurev-cellbio-100913-013512
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error