Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1979 Sep;76(9):4511–4515. doi: 10.1073/pnas.76.9.4511

Murine erythroleukemia cell differentiation: relationship of globin gene expression and of prolongation of G1 to inducer effects during G1/early S.

R Gambari, P A Marks, R A Rifkind
PMCID: PMC411607  PMID: 291983

Abstract

Murine erythroleukemia cells (MELC) are induced to erythroid differentiation by culture with 4 mM hexamethylenebisacetamide. The relationship between onset of accumulation of globin mRNA and cell cycle phase has been examined in MELC fractionated with respect to cell cycle (G1, early S, mid S, and late S/G2) by the technique of centrifugal elutriation. This technique provides synchronized populations of cells without use of chemicals that block cell function (e.g., DNA synthesis). It is shown that the initial onset of accumulation of globin mRNA occurs during the first G1 phase after a complete S traversed in culture with inducer. Once globin mRNA synthesis is initiated, it continues throughout the cell cycle. Studies of synchronized MELC populations exposed to hexamethylenebisacetamide starting in G1, mid S, or late S/G2, provide evidence that an effect of the inducer during G1 or early S is critical to initiation of accumulation of newly synthesized globin mRNA and to the prolongation of G1, both of which are associated with terminal erythroid differentiation.

Full text

PDF
4514

Selected References

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

  1. Bastos R. N., Aviv H. Globin RNA precursor molecules: biosynthesis and process in erythroid cells. Cell. 1977 Jul;11(3):641–650. doi: 10.1016/0092-8674(77)90081-2. [DOI] [PubMed] [Google Scholar]
  2. Brown E. H., Schildkraut C. L. Perturbation of growth and differentiation of Friend murine erythroleukemia cells by 5-bromodeoxyuridine incorporation in early S phase. J Cell Physiol. 1979 May;99(2):261–278. doi: 10.1002/jcp.1040990213. [DOI] [PubMed] [Google Scholar]
  3. Chang H. L., Baserga R. Time of replication of genes responsible for a temperature-sensitive function in a cell cycle-specific ts mutant from a hamster cell line. J Cell Physiol. 1977 Sep;92(3):333–343. doi: 10.1002/jcp.1040920302. [DOI] [PubMed] [Google Scholar]
  4. Fibach E., Reuben R. C., Rifkind R. A., Marks P. A. Effect of hexamethylene bisacetamide on the commitment to differentiation of murine erythroleukemia cells. Cancer Res. 1977 Feb;37(2):440–444. [PubMed] [Google Scholar]
  5. Gambari R., Terada M., Bank A., Rifkind R. A., Marks P. A. Synthesis of globin mRNA in relation to the cell cycle during induced murine erythroleukemia differentiation. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3801–3804. doi: 10.1073/pnas.75.8.3801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Gazitt Y., Deitch A. D., Marks P. A., Rifkind R. A. Cell volume changes in relation to the cell cycle of differentiating erythroleukemic cells. Exp Cell Res. 1978 Dec;117(2):413–420. doi: 10.1016/0014-4827(78)90154-4. [DOI] [PubMed] [Google Scholar]
  7. Gazitt Y., Reuben R. C., Deitch A. D., Marks P. A., Rifkind R. A. Changes in cyclic adenosine 3':5'-monophosphate levels during induction of differentiation in murine erythroleukemia cells. Cancer Res. 1978 Nov;38(11 Pt 1):3779–3783. [PubMed] [Google Scholar]
  8. Geller R., Levenson R., Housman D. Significance of the cell cycle in commitment of murine erythroleukemia cells to erythroid differentiation. J Cell Physiol. 1978 May;95(2):213–222. doi: 10.1002/jcp.1040950211. [DOI] [PubMed] [Google Scholar]
  9. Gusella J., Geller R., Clarke B., Weeks V., Housman D. Commitment to erythroid differentiation by friend erythroleukemia cells: a stochastic analysis. Cell. 1976 Oct;9(2):221–229. doi: 10.1016/0092-8674(76)90113-6. [DOI] [PubMed] [Google Scholar]
  10. KAJIWARA K., MUELLER G. C. MOLECULAR EVENTS IN THE REPRODUCTION OF ANIMAL CELLS. 3. FRACTIONAL SYNTHESIS OF DEOXYRIBONUCLEIC ACID WITH 5-BROMODEOXYURIDINE AND ITS EFFECT ON CLONING EFFICIENCY. Biochim Biophys Acta. 1964 Nov 15;91:486–493. [PubMed] [Google Scholar]
  11. Kasupski G. J., Mukherjee B. B. Effects of controlled exposure of L cells to bromodeoxyuridine (BUdR). I. Evidence for ordered gene replication during S phase. Exp Cell Res. 1977 May;106(2):327–338. doi: 10.1016/0014-4827(77)90178-1. [DOI] [PubMed] [Google Scholar]
  12. Levy J., Terada M., Rifkind R. A., Marks P. A. Induction of erythroid differentiation by dimethylsulfoxide in cells infected with Friend virus: relationship to the cell cycle. Proc Natl Acad Sci U S A. 1975 Jan;72(1):28–32. doi: 10.1073/pnas.72.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Loritz F., Bernstein A., Miller R. G. Early and late volume changes during erythroid differentiation of cultured Friend leukemic cells. J Cell Physiol. 1977 Mar;90(3):423–437. doi: 10.1002/jcp.1040900306. [DOI] [PubMed] [Google Scholar]
  14. Lough J., Bischoff R. Differential sensitivity to 5-bromodeoxyuridine during the S phase of synchronized myogenic cells. Dev Biol. 1976 Jun;50(2):457–475. doi: 10.1016/0012-1606(76)90165-2. [DOI] [PubMed] [Google Scholar]
  15. Lowenhaupt K., Lingrel J. B. A change in the stability of globin mRNA during the induction of murine erythroleukemia cells. Cell. 1978 Jun;14(2):337–344. doi: 10.1016/0092-8674(78)90119-8. [DOI] [PubMed] [Google Scholar]
  16. Marks P. A., Rifkind R. A. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. doi: 10.1146/annurev.bi.47.070178.002223. [DOI] [PubMed] [Google Scholar]
  17. McClintock P. R., Papaconstantinou J. Regulation of hemoglobin synthesis in a murine erythroblastic leukemic cell: the requirement for replication to induce hemoglobin synthesis. Proc Natl Acad Sci U S A. 1974 Nov;71(11):4551–4555. doi: 10.1073/pnas.71.11.4551. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Meistrich M. L., Meyn R. E., Barlogie B. Synchronization of mouse L-P59 cells by centrifugal elutriation separation. Exp Cell Res. 1977 Mar 1;105(1):169–177. doi: 10.1016/0014-4827(77)90163-x. [DOI] [PubMed] [Google Scholar]
  19. Mitchell B. F., Tupper J. T. Synchronization of mouse 3T3 and SV40 3T3 cells by way of centrifugal elutriation. Exp Cell Res. 1977 May;106(2):351–355. doi: 10.1016/0014-4827(77)90180-x. [DOI] [PubMed] [Google Scholar]
  20. Nudel U., Salmon J., Fibach E., Terada M., Rifkind R., Marks P. A., Bank A. Accumulation of alpha- and beta-globin messenger RNAs in mouse erythroleukemia cells. Cell. 1977 Oct;12(2):463–469. doi: 10.1016/0092-8674(77)90122-2. [DOI] [PubMed] [Google Scholar]
  21. Ohta Y., Tanaka M., Terada M., Miller O. J., Bank A., Marks P., Rifkind R. A. Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1232–1236. doi: 10.1073/pnas.73.4.1232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ostertag W., Melderis H., Steinheider G., Kluge N., Dube S. Synthesis of mouse haemoglobin and globin mRNA in leukaemic cell cultures. Nat New Biol. 1972 Oct 25;239(95):231–234. doi: 10.1038/newbio239231a0. [DOI] [PubMed] [Google Scholar]
  23. Reuben R. C., Wife R. L., Breslow R., Rifkind R. A., Marks P. A. A new group of potent inducers of differentiation in murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1976 Mar;73(3):862–866. doi: 10.1073/pnas.73.3.862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ross J., Ikawa Y., Leder P. Globin messenger-RNA induction during erythroid differentiation of cultured leukemia cells. Proc Natl Acad Sci U S A. 1972 Dec;69(12):3620–3623. doi: 10.1073/pnas.69.12.3620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scher W., Friend C. Breakage of DNA and alterations in folded genomes by inducers of differentiation in Friend erythroleukemic cells. Cancer Res. 1978 Mar;38(3):841–849. [PubMed] [Google Scholar]
  26. Terada M., Epner E., Nudel U., Salmon J., Fibach E., Rifkind R. A., Marks P. A. Induction of murine erythroleukemia differentiation by actinomycin D. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2795–2799. doi: 10.1073/pnas.75.6.2795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Terada M., Fried J., Nudel U., Rifkind R. A., Marks P. A. Transient inhibition of initiation of S-phase associated with dimethyl sulfoxide induction of murine erythroleukemia cells to erythroid differentiation. Proc Natl Acad Sci U S A. 1977 Jan;74(1):248–252. doi: 10.1073/pnas.74.1.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Terada M., Nudel U., Fibach E., Rifkind R. A., Marks P. A. Changes in DNA associated with induction of erythroid differentiation by dimethyl sulfoxide in murine erythroleukemia cells. Cancer Res. 1978 Mar;38(3):835–840. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES