John
Frenster, Editor
1. Current Euchromatin
Research Results:
2. Introduction:
3. Heterochromatin and Euchromatin: The First 50
years (1928-1978):
4. Historical Euchromatin References:
5. Reviews
of Activator RNA Research
:
6. Current
Activator RNA Research:
7. Ultrastructural
Probes of DNase I-Sensitive Sites:
8. RNA as
a Therapeutic Agent:
9. Medical Systems
Biology:
10. Hodgkin Lymphoma
Immuno-Pathology:
11. Activated T-Lymphocyte
Immunotherapy:
12. Selective
Gene Transcription:
13. RNA-Induced
Epigenetics:
14. RNA-Induced
Embryogenesis:
15. RNA and Biological
Causality:
16. Reprogramming
and Neoplasia:
17. Ultrastructural
Probes of Active DNA Sites, and the RNA Activators of DNA:
18. A
Brief History of Activator RNA:
Dedicated to the memory of Peyton Rous, discoverer of a viral cause of cancer in 1911.
The Euchromatin Network is designed to help researchers and others interested in the latest developments in our studies of this most active part of the genome within the cell nucleus.
With increasing accuracy, resolution, and sensitivity, our cell biology methods are revealing new and important information about the role of active euchromatin in the life of the cell, during embryogenesis and cell differentiation, during the hormone response and the immune response, during neoplasia and organ regeneration.
Proteins have been described as the "agents" whereby the cell accomplishes its many metabolic functions. DNA has been described as the "library" whereby the cell stores the structural blueprints for each protein of that individual. RNA is now being recognized as the "spark" whereby the cell activates specific genes of the genome for expression in the cell. Such "riboregulators" are being recognized in the animal, the plant, and the bacterial world, even being used as therapeutic agents in human disease.
Euchromatin is that unique combination of DNA, RNA and proteins which allows this magnificent cellular program within the cell nucleus to proceed with accuracy, safety and flexibility.
We invite you to use this network to inform your colleagues, and to learn from them in turn.
Brief History of Heterochromatin and Euchromatin: The first 50 years (1928-1978).
Recent progress in the study of the cell nucleus has increased the long-standing interest in heterochromatin and euchromatin. Heitz (1929) originally described as heterochromatin that portion of the nuclear chromatin which demonstrated its allocycly by maintaining a condensed state while the remainder of the nuclear chromatin was extending to what he termed the euchromatin state.
Cooper (1959) was able to summarize the data from Drosophila which suggested that heterochromatin and euchromatin differed in their biophysical conformations and in metabolic expression of their genes but not in their basic structure of DNA arranged within chromosomes.
Since that time, increasingly detailed genetic studies of the heterochromatic X chromosome of female mammalian cells (Lyon, 1961; Grumbach et al, 1963; Brown and Chandra, 1973), of the heterochromatic paternal chromosomes of coccids (Brown and Nur, 1964), and of the heterochromatic regions of the Y chromosome in Drosophila (Hess and Meyer, 1963) have revealed that the genes within heterochromatin are repressed but can later be expressed when the heterochromatic region undergoes a transition to euchromatin.
Similarly, cytological studies have revealed that heterochromatin displays late replication of its DNA (Lima-De-Faria, 1959), displays no uptake of the DNA ligand acridine orange (Frenster, 1971), and displays little or no synthesis of RNA (Hsu, 1962; Littau et al, 1964; Klevecz and Hsu, 1964), all of which are reversed when heterochromatin is converted to euchromatin, which then displays uptake of the DNA ligand acridine orange with marked hypersensitivity to DNaseI digestion (Frenster, 1971). Euchromatin 10nm (100 A.) microfibrils are ultrastructurally continuous with those in heterochromatin condensations (Frenster, 1965a), and are present in all diploid interphase animal cells examined (Frenster et al, 1974).
Finally, isolation of heterochromatin and euchromatin fractions from the nuclei of mammalian cells (Frenster et al, 1963); McConaughy and McCarthy, 1972) has permitted a direct biochemical and biophysical assay of chromatin DNA template activity in RNA synthesis either before or after such isolation (Frenster, 1965b) again demonstrating that template restriction reflects repression of DNA molecules within heterochromatin, which is reversed when heterochromatin is converted to euchromatin.
These genetic, cytological, biochemical and biophysical studies all strongly support the current view that heterochromatin represents repressed segments of chromosomal DNA while euchromatin represents active segments, and are an expression of the degree of nuclear differentiation within individual differentiated cells (Frenster, 1972; Nakatsu et al, 1974: Frenster, 1974).
Recently, the focus of research on euchromatin has been the RNAs, lipids and proteins (Frenster et al, 1960, 1961; Frenster, 1965b; Rose and Frenster, 1965) involved in the active control of euchromatin within the cell nucleus, see: (Current Research).
References, The first 50 years: (1928-1978):
Allfrey VG, Mirsky AE, (1958), Proc. Natl. Acad. Sci. U.S. 44: 981.
Allfrey VG, (1963), Exp. Cell Res. Suppl. 9: 183.
Allfrey VG, et al, (1963), Proc. Natl. Acad. Sci. U.S. 49: 414.
Allfrey VG, et al, (1964), Proc. Natl. Acad. Sci. U.S. 51: 786.
Anderson NG, et al, (1972), in: "Embryonic
and Fetal Antigens in Cancer", Vol. 2, NTIS.
Archibald RB, Frenster JH, (1973), Natl.
Cancer Inst. Monogr. 36: 239.
Bolund L, et al, (1969), J. Cell Sci. 4: 71.
Bolund L, et al, (1970), Exptl. Cell Res. 62: 76.
Bonner J, et al, (1968), Science 159: 47.
Britten RJ, Davidson EH, (1969), Science
165: 349.
Brown SW, Chandra HS, (1973). Proc. Natl. Acad. Sci. U.S. 70: 195.
Brown SW, Nur U, (1964). Science 145: 130.
Busch H, (1974), in:
"The Cell Nucleus", volumes 1-3 (New York: Academic Press).
Cedar H, Felsenfeld G, (1973), J. Molec. Biol. 77: 237.
Comings DE, (1967). J. Cell Biol. 35: 699.
Cooper KW, (1959). Chromosoma 10: 535.
Crick FHC, (1970a), Nature
227: 561.
Crick FHC, (1970b), Nature 228: 613.
Crick FHC, (1971), Nature 234: 25.
Dahmus ME, Bonner J, (1970), Fed. Proc. 29: 1255.
DeCarvalho S, (1963), Nature
197: 1077.
Fishman WH, (1976), Cancer Research 36: 3423-3428.
Frenster JH et al, (1960). Proc.
Natl. Acad. Sci. U.S. 46: 432.
Frenster JH et al, (1961). Biochim.
Biophys. Acta 47: 130.
Frenster JH, (1963), Exp Cell Res 9, 235-238 (1963).
Frenster JH et al, (1963). Proc.
Natl. Acad. Sci. U.S. 50: 1026.
Frenster JH, (1965a). Nature
205: 1341.
Frenster JH, (1965b). Nature
206: 680.
Frenster JH, (1965c). Nature
206: 1269.
Frenster JH, (1965d), Nature
207: 1139.
Frenster JH, (1965e). Nature
208: 894.
Frenster JH, (1965f). Nature
208: 1093.
Frenster JH, (1965g). in: "The
Chromosome: Structural and Functional Aspects".
Frenster JH, (1966). in: "The Cell Nucleus: Metabolism and Radiosensitivity",
Klouwen HM, ed, pp. 28-49.
Frenster JH, Rogoway WM, (1968). Lancet
2: 979.
Frenster JH, (1969). in: "Handbook of Molecular Cytology", Lima-de-Faria
A, ed, , pp. 251-287
Frenster JH, Rogoway WM, (1970). in: "Proc.
5th Leukocyte Cult. Conf." (Harris JE, ed.): pp. 359-373.
Frenster JH, (1971). Cancer
Res. 31: 1128.
Frenster JH, (1972). Nature
(New Biology) 236: 175.
Frenster JH, (1972), in: "Structure and Functions of the Cell
Nucleus", pp. 159-168, edit. by Zbarsky IB.
Frenster JH, Herstein PR, (1973), in "The
Role of RNA in Reproduction and Development"., pp. 330-338.
Frenster JH, Herstein PR, (1973). New
Eng. J. Med. 288: 1224.
Frenster JH et al, (1974), in "Adv.
Cell and Molec. Biology", vol. 3: pp. 1-19, New York: Academic Press.
Frenster JH, (1974), in "The
Cell Nucleus", (Busch H, ed.) vol. 1: 565-580, New York: Academic Press.
Frenster JH, (1974), in: "Biochemistry of the Cell Nucleus. Mechanism
and Regulation of Gene Expression", Proc.
Ninth Meeting, FEBS, Vol. 33: pp. 419-428.
Frenster JH, (1974), Proc.
11th International Cancer Congress, Florence, Italy.
Frenster JH, (1976), in: "The Role of Nucleic Acid Addition Reactions",
pp. 53-66, edit. by Smith KC.
Frenster JH, (1976), Cancer
Res 36, pp. 3394-3398 (1976).
Frenster JH, et al, (1976), in "Onco-Developmental Gene Expression",
107, Fishman WH, and Sell S, eds.
Gledhill BL, et al, (1966), Exp. Cell Res. 41: 652.
Goldstein L, (1974), Exp. Cell Res. 89: 421.
Grumbach MM et al, (1963). Proc. Natl. Acad. Sci. U.S. 49: 581.
Heitz E, (1928). Jahrb.
wiss. Bot. 69: 762.
Heitz E, (1929). Ber.
Deut. Bot. Ges. 47: 274.
Herstein PR, Frenster JH, (1972), in: "Embryonic
and Fetal Antigens in Cancer", Vol. 2, pp. 5-7, NTIS.
Hess O, Meyer GF, (1963). J. Cell Biol. 16: 527.
Hidvegi EJ, et al , (1974), in: "Biochemistry of the Cell Nucleus.
Mechanism and Regulation of Gene Expression", Proc.
Ninth Meeting, FEBS, Vol. 33: 1.
Holmes DS, and Bonner J, (1974), Proc. Natl. Acad. Sci. U.S. 71:
1108.
Holmes DS, et al, (1974), Biochemistry 13: 849.
Hsu TC, (1962). Exp. Cell Res. 27: 332.
Huang R-CC, Bonner J, (1965), Proc. Natl. Acad. Sci. U.S. 54: 960.
Huang R-CC, Huang PC, (1969), J. Mol. Biol. 39: 365.
Keshgegian AA, et al, (1971), Proc.
4th Ann. Leuk. Cult. Conf. 1969, (McIntyre OR, ed.): pp. 361-366.
Killander D, et al, (1969), Exptl. Cell Res. 54: 163.
Klevecz RR, Hsu TC, (1964), Proc. Natl. Acad. Sci. U.S. 52: 811.
Levy S, et al, (1972), Biochemistry 11: 1547.
Lima-De-Faria A, (1959), J. Biophys. Biochem. Cytol. 6: 1959.
Littau VC et al, (1964). Proc.
Natl. Acad. Sci. U.S. 52: 93.
Lyon MF, (1961). Nature 190: 372.
McConaughy BL, McCarthy BJ, (1972). Biochemistry 11: 998.
Montagnier L, Harel L, (1971), Nature New Biol. 229: 106.
Nakatsu SL et al, (1974).
Nature 248: 334.
Niu MC, Segal SL, (eds), (1973), "The
Role of RNA in Reproduction and Development", pp. 1-357.
Pardon JF, Wilkins MHF, (1972),
J. Molec. Biol. 68: 115.
Paul J, Gilmour RS, (1968), J. Molec. Biol. 34: 305.|
Pederson T, (1974), Proc. Natl. Acad. Sci. U.S., 71: 617.
Rigler R, (1969), Ann. N.Y. Acad. Sci. 157: 211.
Ringertz NR, et al, (1970), Exptl. Cell Res. 62: 204.
Rose HG, Frenster JH, (1965).
Biochim. Biophys. Acta 106: 577.
Segal SJ, Davidson OW, et al, (1965). Proc. Natl. Acad. Sci. U.S.
54: 782.
Simpson RT, Polacow I, (1973), Biochem. Biophys. Res. Commun. 55:
1078.
Stanley DA et al, (1971). in "Proc.
4th Ann. Leukocyte Cult. Conf. 1969," (McIntyre OR, ed.): pp. 1-11.
Yasmineh WG, Yunis JJ, (1973), Exp. Cell Res. 81: 432.
Yerganian G, Dawe CJ, (eds.), (1965), in: "The
Chromosome: Structural and Functional Aspects".