Skip to main content
PMC home page
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
. 1985 Aug;82(15):5020–5024. doi: 10.1073/pnas.82.15.5020

Gene expression during terminal differentiation: dexamethasone suppression of inducer-mediated alpha 1- and beta maj-globin gene expression.

T Kaneda, T Murate, M Sheffery, K Brown, R A Rifkind, P A Marks
PMCID: PMC390490  PMID: 3860841

Abstract

Previous studies demonstrated that hexamethylenebisacetamide (HMBA)-mediated murine erythroleukemia cell (MELC) commitment to terminal division could be suppressed by dexamethasone. A rapid (less than 2 hr) increase (step-up) in commitment to terminal cell division was observed if, after 60-70 hr in culture with inducer and steroid, MELC were transferred to medium with HMBA alone. This step-up commitment was not inhibited by actinomycin or cordycepin but was blocked by cycloheximide. In this study, we show that dexamethasone blocks HMBA-mediated activation of alpha 1- and beta maj-globin gene transcription but not the induced chromatin change characterized by appearance of DNase I-hypersensitive regions upstream from the 5' cap sites of the alpha 1- and beta maj-globin genes. A rapid (less than 2 hr) activation (step-up) of alpha 1-globin gene transcription was observed if, after 48-60 hr in culture with HMBA and dexamethasone, MELC were transferred to medium with HMBA alone. Activation of transcription of the beta maj-globin gene requires 12-24 hr of further culture. Cycloheximide inhibits step-up transcription of both globin genes. Thus, dexamethasone blocks HMBA-mediated modulation of transcription of several nonlinked genes whose expression is altered in a coordinated manner during induced MELC terminal differentiation. Further, the steroid blocks at a late step, a step after that which is rate-limiting to HMBA-mediated MELC differentiation.

Full text

PDF
5020

Images in this article

5022Image
on p.5022
5022Image
on p.5022
5023Image
on p.5023
5023Image
on p.5023

Selected References

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

  1. Burch J. B., Weintraub H. Temporal order of chromatin structural changes associated with activation of the major chicken vitellogenin gene. Cell. 1983 May;33(1):65–76. doi: 10.1016/0092-8674(83)90335-5. [DOI] [PubMed] [Google Scholar]
  2. Charnay P., Treisman R., Mellon P., Chao M., Axel R., Maniatis T. Differences in human alpha- and beta-globin gene expression in mouse erythroleukemia cells: the role of intragenic sequences. Cell. 1984 Aug;38(1):251–263. doi: 10.1016/0092-8674(84)90547-6. [DOI] [PubMed] [Google Scholar]
  3. Chen Z., Banks J., Rifkind R. A., Marks P. A. Inducer-mediated commitment of murine erythroleukemia cells to differentiation: a multistep process. Proc Natl Acad Sci U S A. 1982 Jan;79(2):471–475. doi: 10.1073/pnas.79.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cohen R. B., Sheffery M. Nucleosome disruption precedes transcription and is largely limited to the transcribed domain of globin genes in murine erythroleukemia cells. J Mol Biol. 1985 Mar 5;182(1):109–129. doi: 10.1016/0022-2836(85)90031-2. [DOI] [PubMed] [Google Scholar]
  5. Elgin S. C. DNAase I-hypersensitive sites of chromatin. Cell. 1981 Dec;27(3 Pt 2):413–415. doi: 10.1016/0092-8674(81)90381-0. [DOI] [PubMed] [Google Scholar]
  6. Fantoni A., De la Chapelle A., Rifkind R. A., Marks P. A. Erythroid cell-development in fetal mice: synthetic capacity for different proteins. J Mol Biol. 1968 Apr 14;33(1):79–91. doi: 10.1016/0022-2836(68)90282-9. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Groudine M., Eisenman R., Weintraub H. Chromatin structure of endogenous retroviral genes and activation by an inhibitor of DNA methylation. Nature. 1981 Jul 23;292(5821):311–317. doi: 10.1038/292311a0. [DOI] [PubMed] [Google Scholar]
  9. Hofer E., Darnell J. E., Jr The primary transcription unit of the mouse beta-major globin gene. Cell. 1981 Feb;23(2):585–593. doi: 10.1016/0092-8674(81)90154-9. [DOI] [PubMed] [Google Scholar]
  10. Lo S. C., Aft R., Ross J., Mueller G. C. Control of globin gene expression by steroid hormones in differentiating Friend leukemia cells. Cell. 1978 Oct;15(2):447–453. doi: 10.1016/0092-8674(78)90014-4. [DOI] [PubMed] [Google Scholar]
  11. Marks P. A., Murate T., Kaneda T., Ravetch J., Rifkind R. A. Modulation of gene expression during terminal cell differentiation: murine erythroleukemia. Symp Fundam Cancer Res. 1984;37:327–340. [PubMed] [Google Scholar]
  12. 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]
  13. Mierendorf R. C., Jr, Mueller G. C. Role of dexamethasone in globin gene expression in differentiating Friend cells. J Biol Chem. 1981 Jul 10;256(13):6736–6741. [PubMed] [Google Scholar]
  14. Murate T., Kaneda T., Rifkind R. A., Marks P. A. Inducer-mediated commitment of murine erythroleukemia cells to terminal cell division: the expression of commitment. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3394–3398. doi: 10.1073/pnas.81.11.3394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nishioka Y., Leder P. The complete sequence of a chromosomal mouse alpha--globin gene reveals elements conserved throughout vertebrate evolution. Cell. 1979 Nov;18(3):875–882. doi: 10.1016/0092-8674(79)90139-9. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Osborne H. B., Bakke A. C., Yu J. Effect of dexamethasone on hexamethylene bisacetamide-induced Friend cell erythrodifferentiation. Cancer Res. 1982 Feb;42(2):513–518. [PubMed] [Google Scholar]
  18. Profous-Juchelka H. R., Reuben R. C., Marks P. A., Rifkind R. A. Transcriptional and post-transcriptional regulation of globin gene accumulation in murine erythroleukemia cells. Mol Cell Biol. 1983 Feb;3(2):229–232. doi: 10.1128/mcb.3.2.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Santoro M. G., Benedetto A., Jaffe B. M. Hydrocortisone inhibits DMSO - induced differentiation of Friend erythroleukemia cells. Biochem Biophys Res Commun. 1978 Dec 29;85(4):1510–1517. doi: 10.1016/0006-291x(78)91174-9. [DOI] [PubMed] [Google Scholar]
  21. Scher W., Tsuei D., Sassa S., Price P., Gabelman N., Friend C. Inhibition of dimethyl sulfoxide-stimulated Friend cell erythrodifferentiation by hydrocortisone and other steroids. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3851–3855. doi: 10.1073/pnas.75.8.3851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sheffery M., Marks P. A., Rifkind R. A. Gene expression in murine erythroleukemia cells. Transcriptional control and chromatin structure of the alpha 1-globin gene. J Mol Biol. 1984 Feb 5;172(4):417–436. doi: 10.1016/s0022-2836(84)80015-7. [DOI] [PubMed] [Google Scholar]
  23. Sheffery M., Rifkind R. A., Marks P. A. Murine erythroleukemia cell differentiation: DNase I hypersensitivity and DNA methylation near the globin genes. Proc Natl Acad Sci U S A. 1982 Feb;79(4):1180–1184. doi: 10.1073/pnas.79.4.1180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith R. D., Yu J. Alterations in globin gene chromatin conformation during murine erythroleukemia cell differentiation. J Biol Chem. 1984 Apr 10;259(7):4609–4615. [PubMed] [Google Scholar]
  25. TILL J. E., MCCULLOCH E. A., SIMINOVITCH L. A STOCHASTIC MODEL OF STEM CELL PROLIFERATION, BASED ON THE GROWTH OF SPLEEN COLONY-FORMING CELLS. Proc Natl Acad Sci U S A. 1964 Jan;51:29–36. doi: 10.1073/pnas.51.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tsiftsoglou A. S., Gusella J. F., Volloch V., Housman D. E. Inhibition by dexamethasone of commitment to erythroid differentiation in murine erythroleukemia cells. Cancer Res. 1979 Oct;39(10):3849–3855. [PubMed] [Google Scholar]
  27. Wu C. The 5' ends of Drosophila heat shock genes in chromatin are hypersensitive to DNase I. Nature. 1980 Aug 28;286(5776):854–860. doi: 10.1038/286854a0. [DOI] [PubMed] [Google Scholar]
  28. Yu J., Smith R. D. Sequential alterations in globin gene chromatin structure during erythroleukemia cell differentiation. J Biol Chem. 1985 Mar 10;260(5):3035–3040. [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