Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1986 Feb;6(2):425–440. doi: 10.1128/mcb.6.2.425

Multiple transcription start sites, DNase I-hypersensitive sites, and an opposite-strand exon in the 5' region of the CHO dhfr gene.

P J Mitchell, A M Carothers, J H Han, J D Harding, E Kas, L Venolia, L A Chasin
PMCID: PMC367531  PMID: 3023846

Abstract

Transcription of the 26-kilobase (kb) dihydrofolate reductase (dhfr) gene in CHO cells is initiated at two sites: a major site (approximately 85% of the dhfr mRNA) at -63 relative to the translation start and a minor site (approximately 15%) at -107. Transcription also occurs from the opposite DNA strand in the dhfr 5' region, with a probable initiation site at approximately -195 relative to the dhfr translation start. A 4-kb polyadenylated RNA that is derived from the opposite-strand transcription increases threefold in abundance after serum starvation of CHO cells for 24 h. dhfr mRNA levels do not change during this time. The first dhfr exon lies within a 1-kb genomic region marked by exceptionally high G + C content and lack of DNA methylation. This region also includes a 214-base-pair (bp) exon for the opposite-strand transcript and five of the six DNase I-hypersensitive sites identified at the dhfr locus. Analysis of the DNA sequences of hamster, human (M. Chen, T. Shimada, A. D. Moulton, A. Cline, R. K. Humphries, J. Maizel, and A. W. Nienhuis, J. Biol. Chem. 259:3933-3943, 1984), and mouse (M. McGrogan, C. C. Simonsen, D. T. Smouse, P. J. Farnham, and R. T. Schimke, J. Biol. Chem. 260:2307-2314, 1985) dhfr genes reveals the presence of a 29-bp unit that is conserved 45 to 49 bp upstream of major and minor dhfr transcription start sites. This unit follows the consensus: GRGGCGGTGGCCTNNNNTGTCRCAARTRGGTR. The 5' part of the 29-bp unit contains a GC box that agrees with the GGGCGG consensus-binding site for the RNA polymerase II transcription factor Sp1 (D. Gidoni, W. A. Dynan, and R. Tjian, Nature (London) 312:409-413, 1984). Each of the three mammalian dhfr genes has several G-rich GC boxes proximal to the major dhfr transcription start site and several GC boxes of the opposite orientation (C rich) in a distal region about 500 bp upstream.

Full text

PDF
425

Images in this article

430Image
on p.430
431Image
on p.431
432Image
on p.432
433Image
on p.433
434Image
on p.434

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baty D., Barrera-Saldana H. A., Everett R. D., Vigneron M., Chambon P. Mutational dissection of the 21 bp repeat region of the SV40 early promoter reveals that it contains overlapping elements of the early-early and late-early promoters. Nucleic Acids Res. 1984 Jan 25;12(2):915–932. doi: 10.1093/nar/12.2.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bird A., Taggart M., Frommer M., Miller O. J., Macleod D. A fraction of the mouse genome that is derived from islands of nonmethylated, CpG-rich DNA. Cell. 1985 Jan;40(1):91–99. doi: 10.1016/0092-8674(85)90312-5. [DOI] [PubMed] [Google Scholar]
  4. Brady J., Radonovich M., Thoren M., Das G., Salzman N. P. Simian virus 40 major late promoter: an upstream DNA sequence required for efficient in vitro transcription. Mol Cell Biol. 1984 Jan;4(1):133–141. doi: 10.1128/mcb.4.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Burke J. F. High-sensitivity S1 mapping with single-stranded [32P]DNA probes synthesized from bacteriophage M13mp templates. Gene. 1984 Oct;30(1-3):63–68. doi: 10.1016/0378-1119(84)90105-7. [DOI] [PubMed] [Google Scholar]
  6. Busslinger M., Hurst J., Flavell R. A. DNA methylation and the regulation of globin gene expression. Cell. 1983 Aug;34(1):197–206. doi: 10.1016/0092-8674(83)90150-2. [DOI] [PubMed] [Google Scholar]
  7. Carothers A. M., Urlaub G., Ellis N., Chasin L. A. Structure of the dihydrofolate reductase gene in Chinese hamster ovary cells. Nucleic Acids Res. 1983 Apr 11;11(7):1997–2012. doi: 10.1093/nar/11.7.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Chen M. J., Shimada T., Moulton A. D., Cline A., Humphries R. K., Maizel J., Nienhuis A. W. The functional human dihydrofolate reductase gene. J Biol Chem. 1984 Mar 25;259(6):3933–3943. [PubMed] [Google Scholar]
  9. Coderre J. A., Beverley S. M., Schimke R. T., Santi D. V. Overproduction of a bifunctional thymidylate synthetase-dihydrofolate reductase and DNA amplification in methotrexate-resistant Leishmania tropica. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2132–2136. doi: 10.1073/pnas.80.8.2132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coon H. G., Weiss M. C. A quantitative comparison of formation of spontaneous and virus-produced viable hybrids. Proc Natl Acad Sci U S A. 1969 Mar;62(3):852–859. doi: 10.1073/pnas.62.3.852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Crouse G. F., Leys E. J., McEwan R. N., Frayne E. G., Kellems R. E. Analysis of the mouse dhfr promoter region: existence of a divergently transcribed gene. Mol Cell Biol. 1985 Aug;5(8):1847–1858. doi: 10.1128/mcb.5.8.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Crouse G. F., McEwan R. N., Pearson M. L. Expression and amplification of engineered mouse dihydrofolate reductase minigenes. Mol Cell Biol. 1983 Feb;3(2):257–266. doi: 10.1128/mcb.3.2.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Crouse G. F., Simonsen C. C., McEwan R. N., Schimke R. T. Structure of amplified normal and variant dihydrofolate reductase genes in mouse sarcoma S180 cells. J Biol Chem. 1982 Jul 10;257(13):7887–7897. [PubMed] [Google Scholar]
  14. Dush M. K., Sikela J. M., Khan S. A., Tischfield J. A., Stambrook P. J. Nucleotide sequence and organization of the mouse adenine phosphoribosyltransferase gene: presence of a coding region common to animal and bacterial phosphoribosyltransferases that has a variable intron/exon arrangement. Proc Natl Acad Sci U S A. 1985 May;82(9):2731–2735. doi: 10.1073/pnas.82.9.2731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dynan W. S., Saffer J. D., Lee W. S., Tjian R. Transcription factor Sp1 recognizes promoter sequences from the monkey genome that are simian virus 40 promoter. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4915–4919. doi: 10.1073/pnas.82.15.4915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Dynan W. S., Tjian R. Control of eukaryotic messenger RNA synthesis by sequence-specific DNA-binding proteins. 1985 Aug 29-Sep 4Nature. 316(6031):774–778. doi: 10.1038/316774a0. [DOI] [PubMed] [Google Scholar]
  17. Dynan W. S., Tjian R. Isolation of transcription factors that discriminate between different promoters recognized by RNA polymerase II. Cell. 1983 Mar;32(3):669–680. doi: 10.1016/0092-8674(83)90053-3. [DOI] [PubMed] [Google Scholar]
  18. Dynan W. S., Tjian R. The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter. Cell. 1983 Nov;35(1):79–87. doi: 10.1016/0092-8674(83)90210-6. [DOI] [PubMed] [Google Scholar]
  19. Emerson B. M., Felsenfeld G. Specific factor conferring nuclease hypersensitivity at the 5' end of the chicken adult beta-globin gene. Proc Natl Acad Sci U S A. 1984 Jan;81(1):95–99. doi: 10.1073/pnas.81.1.95. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Emerson B. M., Lewis C. D., Felsenfeld G. Interaction of specific nuclear factors with the nuclease-hypersensitive region of the chicken adult beta-globin gene: nature of the binding domain. Cell. 1985 May;41(1):21–30. doi: 10.1016/0092-8674(85)90057-1. [DOI] [PubMed] [Google Scholar]
  21. Everett R. D., Baty D., Chambon P. The repeated GC-rich motifs upstream from the TATA box are important elements of the SV40 early promoter. Nucleic Acids Res. 1983 Apr 25;11(8):2447–2464. doi: 10.1093/nar/11.8.2447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Farnham P. J., Abrams J. M., Schimke R. T. Opposite-strand RNAs from the 5' flanking region of the mouse dihydrofolate reductase gene. Proc Natl Acad Sci U S A. 1985 Jun;82(12):3978–3982. doi: 10.1073/pnas.82.12.3978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Farnham P. J., Schimke R. T. Transcriptional regulation of mouse dihydrofolate reductase in the cell cycle. J Biol Chem. 1985 Jun 25;260(12):7675–7680. [PubMed] [Google Scholar]
  24. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  25. Flintoff W. F., Weber M. K., Nagainis C. R., Essani A. K., Robertson D., Salser W. Overproduction of dihydrofolate reductase and gene amplification in methotrexate-resistant Chinese hamster ovary cells. Mol Cell Biol. 1982 Mar;2(3):275–285. doi: 10.1128/mcb.2.3.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Fritton H. P., Sippel A. E., Igo-Kemenes T. Nuclease-hypersensitive sites in the chromatin domain of the chicken lysozyme gene. Nucleic Acids Res. 1983 Jun 11;11(11):3467–3485. doi: 10.1093/nar/11.11.3467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gerard R. D., Montelone B. A., Walter C. F., Innis J. W., Scott W. A. Role of specific simian virus 40 sequences in the nuclease-sensitive structure in viral chromatin. Mol Cell Biol. 1985 Jan;5(1):52–58. doi: 10.1128/mcb.5.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Gidoni D., Dynan W. S., Tjian R. Multiple specific contacts between a mammalian transcription factor and its cognate promoters. 1984 Nov 29-Dec 5Nature. 312(5993):409–413. doi: 10.1038/312409a0. [DOI] [PubMed] [Google Scholar]
  29. Groudine M., Casimir C. Post-transcriptional regulation of the chicken thymidine kinase gene. Nucleic Acids Res. 1984 Feb 10;12(3):1427–1446. doi: 10.1093/nar/12.3.1427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. HAM R. G. CLONAL GROWTH OF MAMMALIAN CELLS IN A CHEMICALLY DEFINED, SYNTHETIC MEDIUM. Proc Natl Acad Sci U S A. 1965 Feb;53:288–293. doi: 10.1073/pnas.53.2.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Hendrickson S. L., Wu J. S., Johnson L. F. Cell cycle regulation of dihydrofolate reductase mRNA metabolism in mouse fibroblasts. Proc Natl Acad Sci U S A. 1980 Sep;77(9):5140–5144. doi: 10.1073/pnas.77.9.5140. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Jackson P. D., Felsenfeld G. A method for mapping intranuclear protein-DNA interactions and its application to a nuclease hypersensitive site. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2296–2300. doi: 10.1073/pnas.82.8.2296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jones K. A., Tjian R. Sp1 binds to promoter sequences and activates herpes simplex virus 'immediate-early' gene transcription in vitro. Nature. 1985 Sep 12;317(6033):179–182. doi: 10.1038/317179a0. [DOI] [PubMed] [Google Scholar]
  34. Jones K. A., Yamamoto K. R., Tjian R. Two distinct transcription factors bind to the HSV thymidine kinase promoter in vitro. Cell. 1985 Sep;42(2):559–572. doi: 10.1016/0092-8674(85)90113-8. [DOI] [PubMed] [Google Scholar]
  35. Jongstra J., Reudelhuber T. L., Oudet P., Benoist C., Chae C. B., Jeltsch J. M., Mathis D. J., Chambon P. Induction of altered chromatin structures by simian virus 40 enhancer and promoter elements. Nature. 1984 Feb 23;307(5953):708–714. doi: 10.1038/307708a0. [DOI] [PubMed] [Google Scholar]
  36. Keshet I., Yisraeli J., Cedar H. Effect of regional DNA methylation on gene expression. Proc Natl Acad Sci U S A. 1985 May;82(9):2560–2564. doi: 10.1073/pnas.82.9.2560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kwoh T. J., Engler J. A. The nucleotide sequence of the chicken thymidine kinase gene and the relationship of its predicted polypeptide to that of the vaccinia virus thymidine kinase. Nucleic Acids Res. 1984 May 11;12(9):3959–3971. doi: 10.1093/nar/12.9.3959. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Leys E. J., Kellems R. E. Control of dihydrofolate reductase messenger ribonucleic acid production. Mol Cell Biol. 1981 Nov;1(11):961–971. doi: 10.1128/mcb.1.11.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Masters J. N., Attardi G. Discrete human dihydrofolate reductase gene transcripts present in polysomal RNA map with their 5' ends several hundred nucleotides upstream of the main mRNA start site. Mol Cell Biol. 1985 Mar;5(3):493–500. doi: 10.1128/mcb.5.3.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. McClelland M., Ivarie R. Asymmetrical distribution of CpG in an 'average' mammalian gene. Nucleic Acids Res. 1982 Dec 11;10(23):7865–7877. doi: 10.1093/nar/10.23.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. McGrogan M., Simonsen C. C., Smouse D. T., Farnham P. J., Schimke R. T. Heterogeneity at the 5' termini of mouse dihydrofolate reductase mRNAs. Evidence for multiple promoter regions. J Biol Chem. 1985 Feb 25;260(4):2307–2314. [PubMed] [Google Scholar]
  42. McKnight S. L., Kingsbury R. C., Spence A., Smith M. The distal transcription signals of the herpesvirus tk gene share a common hexanucleotide control sequence. Cell. 1984 May;37(1):253–262. doi: 10.1016/0092-8674(84)90321-0. [DOI] [PubMed] [Google Scholar]
  43. Melera P. W., Davide J. P., Hession C. A., Scotto K. W. Phenotypic expression in Escherichia coli and nucleotide sequence of two Chinese hamster lung cell cDNAs encoding different dihydrofolate reductases. Mol Cell Biol. 1984 Jan;4(1):38–48. doi: 10.1128/mcb.4.1.38. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Melera P. W., Hession C. A., Davide J. P., Scotto K. W., Biedler J. L., Meyérs M. B., Shanske S. Antifolate-resistant Chinese Hamster Cells. mRNA directed overproduction of multiple dihydrofolate reductases from a series of independently derived sublines containing amplified dihydrofolate reductase genes. J Biol Chem. 1982 Nov 10;257(21):12939–12949. [PubMed] [Google Scholar]
  45. Melton D. W., Konecki D. S., Brennand J., Caskey C. T. Structure, expression, and mutation of the hypoxanthine phosphoribosyltransferase gene. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2147–2151. doi: 10.1073/pnas.81.7.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Morandi C., Masters J. N., Mottes M., Attardi G. Multiple forms of human dihydrofolate reductase messenger RNA. Cloning and expression in Escherichia coli of their DNA coding sequence. J Mol Biol. 1982 Apr 15;156(3):583–607. doi: 10.1016/0022-2836(82)90268-6. [DOI] [PubMed] [Google Scholar]
  47. Myoda T. T., Lowther S. V., Funanage V. L., Young F. E. Cloning and mapping of the dihydrofolate reductase gene of Bacillus subtilis. Gene. 1984 Jul-Aug;29(1-2):135–143. doi: 10.1016/0378-1119(84)90174-4. [DOI] [PubMed] [Google Scholar]
  48. Nunberg J. H., Kaufman R. J., Schimke R. T., Urlaub G., Chasin L. A. Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line. Proc Natl Acad Sci U S A. 1978 Nov;75(11):5553–5556. doi: 10.1073/pnas.75.11.5553. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Orlofsky A., Chasin L. A. A domain of methylation change at the albumin locus in rat hepatoma cell variants. Mol Cell Biol. 1985 Jan;5(1):214–225. doi: 10.1128/mcb.5.1.214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Ott M. O., Sperling L., Cassio D., Levilliers J., Sala-Trepat J., Weiss M. C. Undermethylation at the 5' end of the albumin gene is necessary but not sufficient for albumin production by rat hepatoma cells in culture. Cell. 1982 Oct;30(3):825–833. doi: 10.1016/0092-8674(82)90287-2. [DOI] [PubMed] [Google Scholar]
  51. Queen C., Lord S. T., McCutchan T. F., Singer M. F. Three segments from the monkey genome that hybridize to simian virus 40 have common structural elements. Mol Cell Biol. 1981 Dec;1(12):1061–1068. doi: 10.1128/mcb.1.12.1061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Reynolds G. A., Basu S. K., Osborne T. F., Chin D. J., Gil G., Brown M. S., Goldstein J. L., Luskey K. L. HMG CoA reductase: a negatively regulated gene with unusual promoter and 5' untranslated regions. Cell. 1984 Aug;38(1):275–285. doi: 10.1016/0092-8674(84)90549-x. [DOI] [PubMed] [Google Scholar]
  53. Richards R. I., Heguy A., Karin M. Structural and functional analysis of the human metallothionein-IA gene: differential induction by metal ions and glucocorticoids. Cell. 1984 May;37(1):263–272. doi: 10.1016/0092-8674(84)90322-2. [DOI] [PubMed] [Google Scholar]
  54. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  55. Saffer J. D., Singer M. F. Transcription from SV 40-like monkey DNA sequences. Nucleic Acids Res. 1984 Jun 11;12(11):4769–4788. doi: 10.1093/nar/12.11.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Santiago C., Collins M., Johnson L. F. In vitro and in vivo analysis of the control of dihydrofolate reductase gene transcription in serum-stimulated mouse fibroblasts. J Cell Physiol. 1984 Jan;118(1):79–86. doi: 10.1002/jcp.1041180114. [DOI] [PubMed] [Google Scholar]
  58. Searle P. F., Davison B. L., Stuart G. W., Wilkie T. M., Norstedt G., Palmiter R. D. Regulation, linkage, and sequence of mouse metallothionein I and II genes. Mol Cell Biol. 1984 Jul;4(7):1221–1230. doi: 10.1128/mcb.4.7.1221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Setzer D. R., McGrogan M., Schimke R. T. Nucleotide sequence surrounding multiple polyadenylation sites in the mouse dihydrofolate reductase gene. J Biol Chem. 1982 May 10;257(9):5143–5147. [PubMed] [Google Scholar]
  60. Shih C. K., Linial M., Goodenow M. M., Hayward W. S. Nucleotide sequence 5' of the chicken c-myc coding region: localization of a noncoding exon that is absent from myc transcripts in most avian leukosis virus-induced lymphomas. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4697–4701. doi: 10.1073/pnas.81.15.4697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Shimada T., Nienhuis A. W. Only the promoter region of the constitutively expressed normal and amplified human dihydrofolate reductase gene is DNase I hypersensitive and undermethylated. J Biol Chem. 1985 Feb 25;260(4):2468–2474. [PubMed] [Google Scholar]
  62. Siebenlist U., Hennighausen L., Battey J., Leder P. Chromatin structure and protein binding in the putative regulatory region of the c-myc gene in Burkitt lymphoma. Cell. 1984 Jun;37(2):381–391. doi: 10.1016/0092-8674(84)90368-4. [DOI] [PubMed] [Google Scholar]
  63. Singer-Sam J., Keith D. H., Tani K., Simmer R. L., Shively L., Lindsay S., Yoshida A., Riggs A. D. Sequence of the promoter region of the gene for human X-linked 3-phosphoglycerate kinase. Gene. 1984 Dec;32(3):409–417. doi: 10.1016/0378-1119(84)90016-7. [DOI] [PubMed] [Google Scholar]
  64. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  65. Stein R., Sciaky-Gallili N., Razin A., Cedar H. Pattern of methylation of two genes coding for housekeeping functions. Proc Natl Acad Sci U S A. 1983 May;80(9):2422–2426. doi: 10.1073/pnas.80.9.2422. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Tykocinski M. L., Max E. E. CG dinucleotide clusters in MHC genes and in 5' demethylated genes. Nucleic Acids Res. 1984 May 25;12(10):4385–4396. doi: 10.1093/nar/12.10.4385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Urlaub G., Käs E., Carothers A. M., Chasin L. A. Deletion of the diploid dihydrofolate reductase locus from cultured mammalian cells. Cell. 1983 Jun;33(2):405–412. doi: 10.1016/0092-8674(83)90422-1. [DOI] [PubMed] [Google Scholar]
  68. Valerio D., Duyvesteyn M. G., Dekker B. M., Weeda G., Berkvens T. M., van der Voorn L., van Ormondt H., van der Eb A. J. Adenosine deaminase: characterization and expression of a gene with a remarkable promoter. EMBO J. 1985 Feb;4(2):437–443. doi: 10.1002/j.1460-2075.1985.tb03648.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Vigneron M., Barrera-Saldana H. A., Baty D., Everett R. E., Chambon P. Effect of the 21-bp repeat upstream element on in vitro transcription from the early and late SV40 promoters. EMBO J. 1984 Oct;3(10):2373–2382. doi: 10.1002/j.1460-2075.1984.tb02142.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Wigler M., Perucho M., Kurtz D., Dana S., Pellicer A., Axel R., Silverstein S. Transformation of mammalian cells with an amplifiable dominant-acting gene. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3567–3570. doi: 10.1073/pnas.77.6.3567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Wolf S. F., Migeon B. R. Clusters of CpG dinucleotides implicated by nuclease hypersensitivity as control elements of housekeeping genes. Nature. 1985 Apr 4;314(6010):467–469. doi: 10.1038/314467a0. [DOI] [PubMed] [Google Scholar]
  72. Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
  73. Wu C. Two protein-binding sites in chromatin implicated in the activation of heat-shock genes. Nature. 1984 May 17;309(5965):229–234. doi: 10.1038/309229a0. [DOI] [PubMed] [Google Scholar]
  74. Yang J. K., Masters J. N., Attardi G. Human dihydrofolate reductase gene organization. Extensive conservation of the G + C-rich 5' non-coding sequence and strong intron size divergence from homologous mammalian genes. J Mol Biol. 1984 Jun 25;176(2):169–187. doi: 10.1016/0022-2836(84)90419-4. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES