Abstract
Sequences located several kilobases both 5' and 3' of the stably transcribed portion of several genes hybridize to radio-labeled pure fragments of the alternating sequence poly (dG-dT) (dC-dA) ["poly(GT)"]. The genes include the ribosomal DNA of mouse, rat, and human, and also human glucose-6-phosphate dehydrogenase (G6PD) and mouse hypoxanthine-guanine phosphoribosyl transferase (HPRT). HPRT has additional hybridizing sequences in introns. Fragments that include the hybridizing sequences and up to 300 bp of adjoining DNA show perfect runs of poly(GT) (greater than 30bp) in all but the human 5' region of rDNA, which shows a somewhat different alternating purine:pyrimidine sequence, poly(GTAT) (36bp). Within 150 bp of these sequences in various instances are found a number of other sequences reported to affect DNA conformation in model systems. Most marked is an enhancement of sequences matching at least 67% to the consensus binding sequence for topoisomerase II. Two to ten-fold less of such sequences were found in other sequenced portions of the nontranscribed spacer or in the transcribed portion of rDNA. The conservation of the locations of tracts of alternating purine:pyrimidine between evolutionarily diverse species is consistent with a possible functional role for these sequences.
Full text
PDF
















Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aiken J. M., Miller F. D., Hagen F., McKenzie D. I., Krawetz S. A., van de Sande J. H., Rattner J. B., Dixon G. H. Tandem repeats of a specific alternating purine-pyrimidine DNA sequence adjacent to protamine genes in the rainbow trout that can exist in the Z form. Biochemistry. 1985 Oct 22;24(22):6268–6276. doi: 10.1021/bi00343a034. [DOI] [PubMed] [Google Scholar]
- Bach R., Grummt I., Allet B. The nucleotide sequence of the initiation region of the ribosomal transcription unit from mouse. Nucleic Acids Res. 1981 Apr 10;9(7):1559–1569. doi: 10.1093/nar/9.7.1559. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bird A. P. CpG-rich islands and the function of DNA methylation. Nature. 1986 May 15;321(6067):209–213. doi: 10.1038/321209a0. [DOI] [PubMed] [Google Scholar]
- Brownell E., Krystal M., Arnheim N. Structure and evolution of human and African ape rDNA pseudogenes. Mol Biol Evol. 1983 Dec;1(1):29–37. doi: 10.1093/oxfordjournals.molbev.a040304. [DOI] [PubMed] [Google Scholar]
- Bullock P., Miller J., Botchan M. Effects of poly[d(pGpT).d(pApC)] and poly[d(pCpG).d(pCpG)] repeats on homologous recombination in somatic cells. Mol Cell Biol. 1986 Nov;6(11):3948–3953. doi: 10.1128/mcb.6.11.3948. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cassidy B. G., Subrahmanyan C. S., Rothblum L. I. The nucleotide sequence of the 5' region of rat 18S rDNA and adjoining spacer. Biochem Biophys Res Commun. 1982 Aug 31;107(4):1571–1576. doi: 10.1016/s0006-291x(82)80179-4. [DOI] [PubMed] [Google Scholar]
- Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
- Cory S., Adams J. M. A very large repeating unit of mouse DNA containing the 18S, 28S and 5.8S rRNA genes. Cell. 1977 Aug;11(4):795–805. doi: 10.1016/0092-8674(77)90292-6. [DOI] [PubMed] [Google Scholar]
- Gardiner-Garden M., Frommer M. CpG islands in vertebrate genomes. J Mol Biol. 1987 Jul 20;196(2):261–282. doi: 10.1016/0022-2836(87)90689-9. [DOI] [PubMed] [Google Scholar]
- Gasser S. M., Laemmli U. K. Cohabitation of scaffold binding regions with upstream/enhancer elements of three developmentally regulated genes of D. melanogaster. Cell. 1986 Aug 15;46(4):521–530. doi: 10.1016/0092-8674(86)90877-9. [DOI] [PubMed] [Google Scholar]
- Gasser S. M., Laroche T., Falquet J., Boy de la Tour E., Laemmli U. K. Metaphase chromosome structure. Involvement of topoisomerase II. J Mol Biol. 1986 Apr 20;188(4):613–629. doi: 10.1016/s0022-2836(86)80010-9. [DOI] [PubMed] [Google Scholar]
- Goldman W. E., Goldberg G., Bowman L. H., Steinmetz D., Schlessinger D. Mouse rDNA: sequences and evolutionary analysis of spacer and mature RNA regions. Mol Cell Biol. 1983 Aug;3(8):1488–1500. doi: 10.1128/mcb.3.8.1488. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonzalez I. L., Gorski J. L., Campen T. J., Dorney D. J., Erickson J. M., Sylvester J. E., Schmickel R. D. Variation among human 28S ribosomal RNA genes. Proc Natl Acad Sci U S A. 1985 Nov;82(22):7666–7670. doi: 10.1073/pnas.82.22.7666. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gonzalez I. L., Schmickel R. D. The human 18S ribosomal RNA gene: evolution and stability. Am J Hum Genet. 1986 Apr;38(4):419–427. [PMC free article] [PubMed] [Google Scholar]
- Grummt I., Maier U., Ohrlein A., Hassouna N., Bachellerie J. P. Transcription of mouse rDNA terminates downstream of the 3' end of 28S RNA and involves interaction of factors with repeated sequences in the 3' spacer. Cell. 1985 Dec;43(3 Pt 2):801–810. doi: 10.1016/0092-8674(85)90253-3. [DOI] [PubMed] [Google Scholar]
- Hamada H., Petrino M. G., Kakunaga T. A novel repeated element with Z-DNA-forming potential is widely found in evolutionarily diverse eukaryotic genomes. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6465–6469. doi: 10.1073/pnas.79.21.6465. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamada H., Seidman M., Howard B. H., Gorman C. M. Enhanced gene expression by the poly(dT-dG).poly(dC-dA) sequence. Mol Cell Biol. 1984 Dec;4(12):2622–2630. doi: 10.1128/mcb.4.12.2622. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hassouna N., Michot B., Bachellerie J. P. The complete nucleotide sequence of mouse 28S rRNA gene. Implications for the process of size increase of the large subunit rRNA in higher eukaryotes. Nucleic Acids Res. 1984 Apr 25;12(8):3563–3583. doi: 10.1093/nar/12.8.3563. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hattori M., Sakaki Y. Dideoxy sequencing method using denatured plasmid templates. Anal Biochem. 1986 Feb 1;152(2):232–238. doi: 10.1016/0003-2697(86)90403-3. [DOI] [PubMed] [Google Scholar]
- Higuchi R., Stang H. D., Browne J. K., Martin M. O., Huot M., Lipeles J., Salser W. Human ribosomal RNA gene spacer sequences are found interspersed elsewhere in the genome. Gene. 1981 Nov;15(2-3):177–186. doi: 10.1016/0378-1119(81)90127-x. [DOI] [PubMed] [Google Scholar]
- Hyrien O., Debatisse M., Buttin G., de Saint Vincent B. R. A hotspot for novel amplification joints in a mosaic of Alu-like repeats and palindromic A + T-rich DNA. EMBO J. 1987 Aug;6(8):2401–2408. doi: 10.1002/j.1460-2075.1987.tb02518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keppel F. Transcribed human ribosomal RNA genes are attached to the nuclear matrix. J Mol Biol. 1986 Jan 5;187(1):15–21. doi: 10.1016/0022-2836(86)90402-x. [DOI] [PubMed] [Google Scholar]
- Koo H. S., Wu H. M., Crothers D. M. DNA bending at adenine . thymine tracts. Nature. 1986 Apr 10;320(6062):501–506. doi: 10.1038/320501a0. [DOI] [PubMed] [Google Scholar]
- Kuehn M., Arnheim N. Nucleotide sequence of the genetically labile repeated elements 5' to the origin of mouse rRNA transcription. Nucleic Acids Res. 1983 Jan 11;11(1):211–224. doi: 10.1093/nar/11.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
- La Volpe A., Simeone A., D'Esposito M., Scotto L., Fidanza V., de Falco A., Boncinelli E. Molecular analysis of the heterogeneity region of the human ribosomal spacer. J Mol Biol. 1985 May 25;183(2):213–223. doi: 10.1016/0022-2836(85)90214-1. [DOI] [PubMed] [Google Scholar]
- Lafer E. M., Sousa R., Rich A. Anti-Z-DNA antibody binding can stabilize Z-DNA in relaxed and linear plasmids under physiological conditions. EMBO J. 1985 Dec 30;4(13B):3655–3660. doi: 10.1002/j.1460-2075.1985.tb04131.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehrman M. A., Goldstein J. L., Russell D. W., Brown M. S. Duplication of seven exons in LDL receptor gene caused by Alu-Alu recombination in a subject with familial hypercholesterolemia. Cell. 1987 Mar 13;48(5):827–835. doi: 10.1016/0092-8674(87)90079-1. [DOI] [PubMed] [Google Scholar]
- Martini G., Toniolo D., Vulliamy T., Luzzatto L., Dono R., Viglietto G., Paonessa G., D'Urso M., Persico M. G. Structural analysis of the X-linked gene encoding human glucose 6-phosphate dehydrogenase. EMBO J. 1986 Aug;5(8):1849–1855. doi: 10.1002/j.1460-2075.1986.tb04436.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McClellan J. A., Palecek E., Lilley D. M. (A-T)n tracts embedded in random sequence DNA--formation of a structure which is chemically reactive and torsionally deformable. Nucleic Acids Res. 1986 Dec 9;14(23):9291–9309. doi: 10.1093/nar/14.23.9291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Michot B., Bachellerie J. P., Raynal F. Sequence and secondary structure of mouse 28S rRNA 5'terminal domain. Organisation of the 5.8S-28S rRNA complex. Nucleic Acids Res. 1982 Sep 11;10(17):5273–5283. doi: 10.1093/nar/10.17.5273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miesfeld R., Krystal M., Arnheim N. A member of a new repeated sequence family which is conserved throughout eucaryotic evolution is found between the human delta and beta globin genes. Nucleic Acids Res. 1981 Nov 25;9(22):5931–5947. doi: 10.1093/nar/9.22.5931. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moreau J., Marcaud L., Maschat F., Kejzlarova-Lepesant J., Lepesant J. A., Scherrer K. A + T-rich linkers define functional domains in eukaryotic DNA. Nature. 1982 Jan 21;295(5846):260–262. doi: 10.1038/295260a0. [DOI] [PubMed] [Google Scholar]
- Nordheim A., Lafer E. M., Peck L. J., Wang J. C., Stollar B. D., Rich A. Negatively supercoiled plasmids contain left-handed Z-DNA segments as detected by specific antibody binding. Cell. 1982 Dec;31(2 Pt 1):309–318. doi: 10.1016/0092-8674(82)90124-6. [DOI] [PubMed] [Google Scholar]
- Nordheim A., Rich A. Negatively supercoiled simian virus 40 DNA contains Z-DNA segments within transcriptional enhancer sequences. Nature. 1983 Jun 23;303(5919):674–679. doi: 10.1038/303674a0. [DOI] [PubMed] [Google Scholar]
- Nordheim A., Rich A. The sequence (dC-dA)n X (dG-dT)n forms left-handed Z-DNA in negatively supercoiled plasmids. Proc Natl Acad Sci U S A. 1983 Apr;80(7):1821–1825. doi: 10.1073/pnas.80.7.1821. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pardue M. L., Lowenhaupt K., Rich A., Nordheim A. (dC-dA)n.(dG-dT)n sequences have evolutionarily conserved chromosomal locations in Drosophila with implications for roles in chromosome structure and function. EMBO J. 1987 Jun;6(6):1781–1789. doi: 10.1002/j.1460-2075.1987.tb02431.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Raynal F., Michot B., Bachellerie J. P. Complete nucleotide sequence of mouse 18 S rRNA gene: comparison with other available homologs. FEBS Lett. 1984 Feb 27;167(2):263–268. doi: 10.1016/0014-5793(84)80139-8. [DOI] [PubMed] [Google Scholar]
- Reeder R. H. Enhancers and ribosomal gene spacers. Cell. 1984 Sep;38(2):349–351. doi: 10.1016/0092-8674(84)90489-6. [DOI] [PubMed] [Google Scholar]
- Rich A., Nordheim A., Wang A. H. The chemistry and biology of left-handed Z-DNA. Annu Rev Biochem. 1984;53:791–846. doi: 10.1146/annurev.bi.53.070184.004043. [DOI] [PubMed] [Google Scholar]
- Rothblum L. I., Reddy R., Cassidy B. Transcription initiation site of rat ribosomal DNA. Nucleic Acids Res. 1982 Nov 25;10(22):7345–7362. doi: 10.1093/nar/10.22.7345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sander M., Hsieh T. S. Drosophila topoisomerase II double-strand DNA cleavage: analysis of DNA sequence homology at the cleavage site. Nucleic Acids Res. 1985 Feb 25;13(4):1057–1072. doi: 10.1093/nar/13.4.1057. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schmid C. W., Jelinek W. R. The Alu family of dispersed repetitive sequences. Science. 1982 Jun 4;216(4550):1065–1070. doi: 10.1126/science.6281889. [DOI] [PubMed] [Google Scholar]
- Stringer J. R. Recombination between poly[d(GT).d(CA)] sequences in simian virus 40-infected cultured cells. Mol Cell Biol. 1985 Jun;5(6):1247–1259. doi: 10.1128/mcb.5.6.1247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas J. R., Bolla R. I., Rumbyrt J. S., Schlessinger D. DNase I-resistant nontranscribed spacer segments of mouse ribosomal DNA contain poly(dG-dT).poly(dA-dC). Proc Natl Acad Sci U S A. 1985 Nov;82(22):7595–7598. doi: 10.1073/pnas.82.22.7595. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Torczynski R. M., Fuke M., Bollon A. P. Cloning and sequencing of a human 18S ribosomal RNA gene. DNA. 1985 Aug;4(4):283–291. doi: 10.1089/dna.1985.4.283. [DOI] [PubMed] [Google Scholar]
- Treco D., Arnheim N. The evolutionarily conserved repetitive sequence d(TG.AC)n promotes reciprocal exchange and generates unusual recombinant tetrads during yeast meiosis. Mol Cell Biol. 1986 Nov;6(11):3934–3947. doi: 10.1128/mcb.6.11.3934. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Udvardy A., Schedl P., Sander M., Hsieh T. S. Topoisomerase II cleavage in chromatin. J Mol Biol. 1986 Sep 20;191(2):231–246. doi: 10.1016/0022-2836(86)90260-3. [DOI] [PubMed] [Google Scholar]
- Urano Y., Kominami R., Mishima Y., Muramatsu M. The nucleotide sequence of the putative transcription initiation site of a cloned ribosomal RNA gene of the mouse. Nucleic Acids Res. 1980 Dec 20;8(24):6043–6058. doi: 10.1093/nar/8.24.6043. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yang-Yen H. F., Subrahmanyam C. S., Cassidy B., Rothblum L. I. Characterization of rat ribosomal DNA II. identification of the highly repetitive DNA in the 3' non-transcribed spacer. J Mol Biol. 1985 Aug 5;184(3):389–398. doi: 10.1016/0022-2836(85)90289-x. [DOI] [PubMed] [Google Scholar]
- Yavachev L. P., Georgiev O. I., Braga E. A., Avdonina T. A., Bogomolova A. E., Zhurkin V. B., Nosikov V. V., Hadjiolov A. A. Nucleotide sequence analysis of the spacer regions flanking the rat rRNA transcription unit and identification of repetitive elements. Nucleic Acids Res. 1986 Mar 25;14(6):2799–2810. doi: 10.1093/nar/14.6.2799. [DOI] [PMC free article] [PubMed] [Google Scholar]


