John H. Frenster ^{1, @} and Jeannette A. Hovsepian ²

Departments of ¹ Medicine and of ² Radiology, Stanford University School of Medicine, Stanford, California  94305, USA,

^@ Present Address: RNA Research, Physicians’ Educational Series, Atherton, CA  94027-5446 USA.
Phone:  +1 650 367 6483;   Fax:  +1 650 364 1773;   e-mail:   frenster@euchromatin.net

* Supported in part by a USPHS Research Career Development Award (CA-17857) from the National Cancer Institute to JHF.

We have studied the ultrastructure of chromosome-chromosome contact points during interphase in mammalian cells, possibly indicating DNA-DNA tetraplex structures which favor the synthesis of paired sense-antisense RNA molecules as in the mouse embryo. The contact points between adjacent interphase chromosomes consist of 20 nm caliber microcylinders formed from two 10 nm caliber euchromatin microfibrils from each of two adjacent chromosomes. Such close apposition of chromatin structures could allow a physical interaction between complementary DNA sequences from each chromosome, which favors a simultaneous transcription of paired sense-antisense RNA from such a DNA tetraplex. Simultaneous paired sense-antisense transcription usually occurs at one gene locus, and may be paired for part or all of the length of each RNA product. Because RNA-RNA duplexes are more stable than DNA-RNA or DNA-DNA duplexes, some of the paired sense-antisense products from one gene locus may appear as RNA-RNA duplexes, and be easily transported to adjacent cells as inducers during embryogenesis.

Kissing Chromosomes Mediate Paired  Sense-Antisense RNA Transcription on a DNA-DNA Tetraplex.

Kioussis D, "Gene regulation: Kissing Chromosomes",  Nature vol. 435, no. 7042, pp. 579-580 (June 2,  2005).

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2. Osborne CS, Chakalova L, Brown KE, Carter D, Horton A, Debrand E, Goyenechea B, Mitchell JA, Lopes S, Reik W, and Fraser P, "Active genes dynamically colocalize to shared sites of ongoing transcription", Nature Genetics, vol. 36, no. 10, pp. 1065-1071 (October, 2004).

3. Frenster JH, and Hovsepian JA, "Ultrastructure  of Closed Loops within Euchromatin of Isolated Lymphocyte Nuclei", Molec. Biol. Cell, vol. 15, suppl., p. 450a (November, 2004).

4. Muller WG, Rieder D, Kreth G, Cremer C, Trajanoski Z, and McNally JG, "Generic Features of Tertiary Chromatin Structure as Detected in Natural Chromosomes", Molec. Cell. Biol., vol. 24, no. 21, pp. 9359-9370 (November, 2004).

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6. Spilianakis CG, Lalioti MD, Town T, Lee GR, and Flavell RA, "Interchromosomal associations between alternatively expressed loci", Nature vol. 435, no. 7042, pp. 637-645 (June 2, 2005).
http://www.nature.com/nature/journal/v435/n7042/abs/nature03574.html

7. Frenster JH, and Hovsepian JA, "Ultrastructure of Euchromatin Contact Points between the Closed Loops of Adjacent Interphase Chromosomes", Molec. Biol. Cell, vol. 16, suppl., p. 1280a (December, 2005).

8. Xu N, Tsai C-L, and Lee JT, "Transient Homologous Pairing Marks the Onset of X Inactivation", Science vol. 311, no. 5764, pp. 1149-1152 (February 24, 2006).

9. Carrel L, "X"-Rated Chromosomal Rendezvous", Science, vol. 311, no. 5764, 1107-1109 (February 24, 2006).

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15. Lanctôt C, Cheutin T, Cremer M, Cavalli G, and Cremer T, "Dynamic genome architecture in the nuclear space:  regulation of gene expression in three dimensions", Nature Reviews Genetics vol. 8, no. 2, pp. 104-115 (February 2007).

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Biochemistry, vol. 11, no. 11, pp. 2020-2026 (May, 1972).

1. Frenster JH, "Selective Control of DNA Helix Openings during Gene Regulation", Cancer Research, vol. 36, pp. 3394-3398 (September, 1976).

2. Hovsepian JA, and Frenster JH, "Sense and Antisense during RNA Initiation of the DNA Transcription Bubble"., Presented at RNA2005, the Tenth Annual Meeting of the RNA Society, Banff, Alberta, Canada, May 24-29, 2005, and published in "RNA2005", p. 279, The RNA Society, Bethesda, MD 20814-3998, (2005).

3. Coudert AE, Pibouin L, Vi-Fane B, Thomas BL, Macdougall M, Choudhury A, Robert B, Sharpe PT, Berda A, and Lezot F, "Expression and regulation of the Msx1 natural antisense transcript during development", Nucleic Acid Research, vol. 33, no. 16, pp. 5208-5216 (2005).

4. Barclay C, Li AW, Geldenhuys L, Baguma-Nibasheka M, Porter GA, Veugelers PJ, Murphy PR, and Casson AG, "Basic Fibroblast Growth Factor (FGF-2) Overexpression Is a Risk Factor for Esophageal Cancer Recurrence and Reduced Survival, which Is Ameliorated by Coexpression of the FGF-2 Antisense Gene",
Clin. Cancer Res., vol. 11, no. 21, 7683-7689 (2005).

5. Frenster JH, "Model of Single-Stranded Integration of Oncogenic Viral Genomes", Biophys. J. vol. 15: 137a (1975).
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E-mail: frenster@euchromatin.net