Presented at the 14th  John  Innes  Symposium, "Chromosome Dynamics and Expression", John Innes Centre, Norwich Research  Park, Colney, Norwich, Norfolk, U.K., Sept. 5-8, 2001, and Published in: "The Fourteenth John Innes Symposium, 5-8 September 2001, Chromosome Dynamics and Expression, Abstracts", p. 51, (John Innes Centre, Norwich, UK, 2001):

"Activation  of  DNA  Transcription  Within  Repressed  Chromatin".

Frenster, J.H.,  Physicians’ Educational Series, Atherton, CA 94027-5446  USA.

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Abstract:

Activation of gene transcription is a complex mechanism of  molecular interactions within the cell nucleus. Repressed and active chromatin fractions were each isolated from the same lymphocytes (Proc. Natl. Acad. Sci. USA  50: 1026 (1963), and were then used to assay  a wide array of  nuclear molecular species as activators of DNA transcription within repressed chromatin. Total nuclear RNA  has significant  activator effect on repressed  heterochromatin, but has little additional effect  on already-active euchromatin. Total cytoplasmic RNA and total yeast RNA  have intermediate and even negative effects on activation. Nuclear translation products (Proc. Natl. Acad. Sci. USA  46: 432 (1960)  also have significant  activation activity, but less than total nuclear RNA, while nuclear ribonucleoprotein particles are still less active (Nature 206: 680 (1965). Some nuclear RNA species are double-stranded and partially- resistant  to RNase. Nuclear histone proteins are uniformly inhibitory to already-active euchromatin. Nuclear RNA species offer the potential for high gene specificity during activation of DNA transcription.

Supported in part by USPHS Research Grants and a Research Career Development Award from the National Cancer Institute.


References:

1. Tseng BY, and Goulian M, "Initiator RNA of Discontinuous DNA Synthesis in Human Lymphocytes", Cell 12: 483 (1977).

2. Frenster JH, "Nuclear Polyanions as De-Repressors of Synthesis of Ribonucleic Acid", Nature 206: 680 (1965).

3. Lanz, RB, McKenna NJ, Onate SA, Albrecht U, Wong J, Tsai SY, Tsai MJ, amd O'Malley BW, "A Steroid Receptor Coactivator, SRA, Functions as an RNA and is Present in a SRC-1 Complex",  Cell 97: 17 (1999).

4. De Carvalho S, "Effect of RNA from Normal Human Marrow on Leukaemic Marrow In-Vivo", Nature 197: 1077 (1963).

5. Frenster JH, Allfrey VG, and Mirsky AE, "Repressed and Active Chromatin Isolated from Interphase Lymphocytes", Proc. Natl. Acad. Sci., USA 50: 1026 (1963).

6. Frenster JH, Allfrey VG, and Mirsky AE, "Metabolism and Morphology of Ribonucleoprotein Particles from the Cell Nucleus of Lymphocytes", Proc. Natl. Acad. Sci., USA 46: 432 (1960).

7. Mishra MC, Niu MC, and Tatum EL, "Induction by RNA of Inositol Independence in Neurospora crassa". Proc. Natl. Acad. Sci. USA 72: 642 (1975).

8. Dobrzelewski J, Mileska Z, and Panusz H, "Effect on Transcription of Low-Molecular-Weight RNA from Calf Thymus Chromatin", Acta Biochim. Pol. 27:  75 (1980).

9. Review: "Selective Gene De-Repression by De-Repressor RNA," in: "Eukaryotic Gene Regulation", Volume 1, pp. 131-143, 1980, edit. Kolodny GM, CRC Press, Boca Raton, FL, USA.

10. Frenster JH, "Oncogenes as Molecular Targets within Active Chromatin", Clin. Cancer Res. 5: suppl. 1, 3855a (1999).

11. Huttenhofer A, Kiefmann M, Meier-Ewert S, O'Brien J, Lehrach H, Bachellerie J-P, and Brosius J, "RNomics: An Experimental Approach that Identifies 201 Candidates for Novel, Small, Non-Messenger RNAs in Mouse", EMBO J. 20: 2943 (2001).

12. Geiss G, Jin E, Guo J, Bumgarner R, Katze MG, and Sen GC, "A Comprehensive View of Regulation of Gene Expression by Double-Stranded RNA-Mediated Cell Signaling", J. Biol. Chem. 276: 30178 (2001).

13. Luo Y, Kurz J, MacAfee N, and Krause MO, "C-myc Deregulation during Transformation Induction: Involvement of 7SK RNA", J. Cell. Biochem. 64: 313-327 (1997).

14. Storz G, "An Expanding Universe of Noncoding RNAs", Science 296: 1260-1263 (2002).

15. Frenster JH, "Nuclear RNA Species Activate DNA Transcription Within Chromatin", FASEB Journal, Vol. 13, No. 7, A1506 (April 23, 1999).


Additional Background Papers (Historical, Molecular, or Cellular):

A: Historical:

A1. Flemming W, "Contributions to the Knowledge of the Cell and Its Vital Processes", Part II, Arch. Mikroskop. Anat. vol. 18, pp. 151-289 (1880). (Reprinted in: J. Cell Biol. vol. 25: pp. 581-589 (1965).

A2. Zacharias H, "Emil Heitz (1892-1965): Chloroplasts, Heterochromatin, and Polytene Chromosomes", Genetics vol. 141, pp. 7-14, (September, 1995).

A3. King TJ, and Briggs R, "Serial Transplantation of Embryonic Nuclei", Cold Spring Harbor Symp. Quant. Biol., vol. 21, pp. 271-290, (1956).

A4. Nanney DL, "Epigenetic Control Systems", Proc. Natl. Acad. Sci. USA, vol. 44, pp. 712-717 (1958).

A5. Brink RA, "Paramutation and Chromosome Organization", Quart. Rev. Biol. , vol. 35, pp. 120-137 (1960).

A6. Grumbach MM, Morishima A, and Taylor JH, "Human Sex Chromatin Abnormalities in Relation to DNA Replication and Heterochromatinization", Proc. Natl. Acad. Sci. USA, vol. 49, pp. 581-589 (1963).

A7. McCarthy BJ, and Hoyer BH, "Identity of DNA and Diversity of Messenger RNA Molecules in Normal Mouse Tissues", Proc. Natl. Acad. Sci. USA, vol. 52: pp. 915-922 (1964).

A8. Crick F, "Central Dogma of Molecular Biology", Nature, vol. 227, pp. 561-563 (August 8, 1970).


B: Molecular:

B0. Stull D, and Pisano JM, "Purely RNA: New Innovations Enhance the Quality, Speed, and Efficiency of RNA Isolation Techniques", The Scientist, vol. 15, no. 22, pp. 29-31 (November 12, 2001).

B1. Frenster JH, "Ultrastructural Continuity Between Active and Repressed Chromatin", Nature vol. 205, no. 4978, pp. 1341-1342, (March 27, 1965).

B2. Frenster JH, "A Model of Specific De-Repression within Interphase Chromatin", Nature vol. 206, no. 4990, pp. 1269-1270, (June 19, 1965).

B3. Frenster JH, "Mechanisms of Repression and De-Repression within Interphase Chromatin", In Vitro vol. 1, pp. 78-101, (1965).

B4. Frenster JH, "Localized Strand Separations within Deoxyribonucleic Acid during Selective Transcription", Nature vol. 208, no. 5013, pp. 894-896, (November 27. 1965).

B5. Frenster JH, "Correlation of the Binding to DNA Loops or to DNA Helices with the Effect on RNA Synthesis", Nature vol. 208, no. 5015, p. 1093, (December 11, 1965).

B6. Frenster JH, "Correlation Between the Ultrastructural Binding Site of Nuclear Ligands and the Effect of the Ligand on RNA Synthesis in Human Leukocytes", J. Cell Biol. vol 47, p. 65a (1970).

B7. Frenster JH, and Herstein PR, "Gene De-Repression", New Eng. J. Med. vol. 288, pp. 1224-1229, (June 7, 1973).

B8. Frenster JH, "Selective Control of DNA Helix Openings during Gene Regulation", Cancer Res. vol. 36, pp. 3394-3398 (September, 1976).


C: Cellular:

C0.  Frenster JH, "Ultrastructural Continuity Between Active and Repressed Chromatin", Nature vol. 205, no. 4978, pp. 1341-1342 (March 27, 1965).

C1. Frenster JH, "Electron Microscopic Localization of Acridine Orange Binding to DNA within Human
Leukemic Bone Marrow Cells", Cancer Res. vol. 31, pp. 1128-1133 (August, 1971).

C2. Frenster JH, Nakatsu SL, and Masek MA, "Ultrastructural Probes of DNA Templates within Human Bone Marrow and Lymph Node Cells", Adv. Cell Molec. Biol. vol. 3, pp. 1-19, (1974).

C3. Nakatsu SL, Masek MA, Landrum S, and Frenster JH, "Activity of DNA Templates During Cell Division and Cell Differentiation", Nature vol. 248, no. 5446, pp. 334-335, (March 22, 1974).

C4. Frenster JH, "Phytohemagglutinin-Activated Autochthonous Lymphocytes for Systemic Immunotherapy of  Human Neoplasms", Ann. N.Y. Acad. Sci. vol. 277, pp. 45-51, (1976).

C5. Frenster JH, Papalian MM, Masek MA, and Frenster JH, "Electron Microscopic Analysis of Lymph Node Cellular Activity in Hodgkin's Disease", J. Natl. Cancer Inst. vol. 63, pp. 331-335, (August, 1979).

C6. Frenster JH, "Electron Microscopic Analysis of Asymmetry within the Cell Nucleus of DNA Helix Openings During Human Cell Activation and Cell Differentiation", "38th Ann. Proc. Electron Microscopy Soc. Amer.", San Francisco, California, 1980, Bailey GW, (ed.), pp. 544-545.

C7. Frenster JH, "Single-Cell Analysis of DNase I-Sensitive Sites during Neoplastic and Normal Cell Differentiation within Human Bone Marrow", Ann. N.Y. Acad. Sci. vol. 567, pp. 334-336, (August, 1989).

C8. Frenster JH, "Oncogenes as Molecular Targets within Active Chromatin", Clin. Cancer Res. vol. 5, suppl. 1, p. 3855s, (624), (November, 1999).

C9. Frenster JH, "Uni-Polar Clustering of Lymphocyte DNA Templates toward Neoplastic Target Cells within Hodgkin's Disease Lymph Nodes", Proc. Am. Assoc. Cancer Res. 43: 1134 (2002).


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euchromatin: "the most active portion of the genome within the cell nucleus".