Abstract
In naturally synchronous plasmodia of Physarum polycephalum, both tubulin and histone gene transcription define periodic cell cycle- regulated events. Using a slot-blot hybridization assay and Northern blot analysis, we have demonstrated that a major peak of accumulation of both alpha-tubulin and histone H4 transcripts occurs in late G2 phase. Nuclear transcription assays indicate that both genes are transcriptionally activated at the same point in the cell cycle: mid G2 phase. While the rate of tubulin gene transcription drops sharply at the M/S-phase boundary, the rate of histone gene transcription remains high through most of S phase. We conclude that the cell cycle regulation of tubulin expression occurs primarily at the level of transcription, while histone regulation involves both transcriptional and posttranscriptional controls. It is possible that the periodic expression of both histone and tubulin genes is triggered by a common cell cycle regulatory mechanism.
Full Text
The Full Text of this article is available as a PDF (831.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alterman R. B., Ganguly S., Schulze D. H., Marzluff W. F., Schildkraut C. L., Skoultchi A. I. Cell cycle regulation of mouse H3 histone mRNA metabolism. Mol Cell Biol. 1984 Jan;4(1):123–132. doi: 10.1128/mcb.4.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ares M., Jr, Howell S. H. Cell cycle stage-specific accumulation of mRNAs encoding tubulin and other polypeptides in Chlamydomonas. Proc Natl Acad Sci U S A. 1982 Sep;79(18):5577–5581. doi: 10.1073/pnas.79.18.5577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ben-Ze'ev A., Farmer S. R., Penman S. Mechanisms of regulating tubulin synthesis in cultured mammalian cells. Cell. 1979 Jun;17(2):319–325. doi: 10.1016/0092-8674(79)90157-0. [DOI] [PubMed] [Google Scholar]
- Bravo R., Celis J. E. A search for differential polypeptide synthesis throughout the cell cycle of HeLa cells. J Cell Biol. 1980 Mar;84(3):795–802. doi: 10.1083/jcb.84.3.795. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Burland T. G., Gull K., Schedl T., Boston R. S., Dove W. F. Cell type-dependent expression of tubulins in Physarum. J Cell Biol. 1983 Dec;97(6):1852–1859. doi: 10.1083/jcb.97.6.1852. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carrino J. J., Laffler T. G. The effect of heat shock on the cell cycle regulation of tubulin expression in Physarum polycephalum. J Cell Biol. 1985 Feb;100(2):642–647. doi: 10.1083/jcb.100.2.642. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleveland D. W., Havercroft J. C. Is apparent autoregulatory control of tubulin synthesis nontranscriptionally regulated? J Cell Biol. 1983 Sep;97(3):919–924. doi: 10.1083/jcb.97.3.919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleveland D. W., Lopata M. A., Sherline P., Kirschner M. W. Unpolymerized tubulin modulates the level of tubulin mRNAs. Cell. 1981 Aug;25(2):537–546. doi: 10.1016/0092-8674(81)90072-6. [DOI] [PubMed] [Google Scholar]
- Cleveland D. W., Pittenger M. F., Feramisco J. R. Elevation of tubulin levels by microinjection suppresses new tubulin synthesis. Nature. 1983 Oct 20;305(5936):738–740. doi: 10.1038/305738a0. [DOI] [PubMed] [Google Scholar]
- Dallman T., Ares M., Jr, Howell S. H. Analysis of transcription during the cell cycle in toluenized Chlamydomonas reinhardi cells. Mol Cell Biol. 1983 Aug;3(8):1537–1539. doi: 10.1128/mcb.3.8.1537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Groudine M., Peretz M., Weintraub H. Transcriptional regulation of hemoglobin switching in chicken embryos. Mol Cell Biol. 1981 Mar;1(3):281–288. doi: 10.1128/mcb.1.3.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hanly S. M., Bleecker G. C., Heintz N. Identification of promoter elements necessary for transcriptional regulation of a human histone H4 gene in vitro. Mol Cell Biol. 1985 Feb;5(2):380–389. doi: 10.1128/mcb.5.2.380. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heintz N., Roeder R. G. Transcription of human histone genes in extracts from synchronized HeLa cells. Proc Natl Acad Sci U S A. 1984 May;81(9):2713–2717. doi: 10.1073/pnas.81.9.2713. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heintz N., Sive H. L., Roeder R. G. Regulation of human histone gene expression: kinetics of accumulation and changes in the rate of synthesis and in the half-lives of individual histone mRNAs during the HeLa cell cycle. Mol Cell Biol. 1983 Apr;3(4):539–550. doi: 10.1128/mcb.3.4.539. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hereford L. M., Osley M. A., Ludwig T. R., 2nd, McLaughlin C. S. Cell-cycle regulation of yeast histone mRNA. Cell. 1981 May;24(2):367–375. doi: 10.1016/0092-8674(81)90326-3. [DOI] [PubMed] [Google Scholar]
- Hereford L., Bromley S., Osley M. A. Periodic transcription of yeast histone genes. Cell. 1982 Aug;30(1):305–310. doi: 10.1016/0092-8674(82)90036-8. [DOI] [PubMed] [Google Scholar]
- Jalouzot R., Toublan B., Wilhelm M. L., Wilhelm F. X. Replication timing of the H4 histone genes in Physarum polycephalum. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6475–6479. doi: 10.1073/pnas.82.19.6475. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Keller L. R., Schloss J. A., Silflow C. D., Rosenbaum J. L. Transcription of alpha- and beta-tubulin genes in vitro in isolated Chlamydomonas reinhardi nuclei. J Cell Biol. 1984 Mar;98(3):1138–1143. doi: 10.1083/jcb.98.3.1138. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Laffler T. G., Chang M. T., Dove W. F. Periodic synthesis of microtubular proteins in the cell cycle of Physarum. Proc Natl Acad Sci U S A. 1981 Aug;78(8):5000–5004. doi: 10.1073/pnas.78.8.5000. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lefebvre P. A., Nordstrom S. A., Moulder J. E., Rosenbaum J. L. Flagellar elongation and shortening in Chlamydomonas. IV. Effects of flagellar detachment, regeneration, and resorption on the induction of flagellar protein synthesis. J Cell Biol. 1978 Jul;78(1):8–27. doi: 10.1083/jcb.78.1.8. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lefebvre P. A., Silflow C. D., Wieben E. D., Rosenbaum J. L. Increased levels of mRNAs for tubulin and other flagellar proteins after amputation or shortening of Chlamydomonas flagella. Cell. 1980 Jun;20(2):469–477. doi: 10.1016/0092-8674(80)90633-9. [DOI] [PubMed] [Google Scholar]
- Minami S. A., Collis P. S., Young E. E., Weeks D. P. Tubulin induction in C. reinhardii: requirement for tubulin mRNA synthesis. Cell. 1981 Apr;24(1):89–95. doi: 10.1016/0092-8674(81)90504-3. [DOI] [PubMed] [Google Scholar]
- Mittermayer C., Braun R., Rusch H. P. Ribonucleic acid synthesis in vitro in nuclei isolated from the synchronously dividing Physarum polycephalum. Biochim Biophys Acta. 1966 Mar 21;114(3):536–546. doi: 10.1016/0005-2787(66)90102-x. [DOI] [PubMed] [Google Scholar]
- Nader W. F., Edlind T. D., Huettermann A., Sauer H. W. Cloning of Physarum actin sequences in an exonuclease-deficient bacterial host. Proc Natl Acad Sci U S A. 1985 May;82(9):2698–2702. doi: 10.1073/pnas.82.9.2698. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Plumb M., Stein J., Stein G. Coordinate regulation of multiple histone mRNAs during the cell cycle in HeLa cells. Nucleic Acids Res. 1983 Apr 25;11(8):2391–2410. doi: 10.1093/nar/11.8.2391. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schedl T., Burland T. G., Gull K., Dove W. F. Cell cycle regulation of tubulin RNA level, tubulin protein synthesis, and assembly of microtubules in Physarum. J Cell Biol. 1984 Jul;99(1 Pt 1):155–165. doi: 10.1083/jcb.99.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schofield P. N., Walker I. O. Control of histone gene expression in Physarum polycephalum. I. Protein synthesis during the cell cycle. J Cell Sci. 1982 Oct;57:139–150. doi: 10.1242/jcs.57.1.139. [DOI] [PubMed] [Google Scholar]
- Silflow C. D., Rosenbaum J. L. Multiple alpha- and beta-tubulin genes in Chlamydomonas and regulation of tubulin mRNA levels after deflagellation. Cell. 1981 Apr;24(1):81–88. doi: 10.1016/0092-8674(81)90503-1. [DOI] [PubMed] [Google Scholar]
- Weeks D. P., Collis P. S. Induction and synthesis of tubulin during the cell cycle and life cycle of Chlamydomonas reinhardi. Dev Biol. 1979 Apr;69(2):400–407. doi: 10.1016/0012-1606(79)90300-2. [DOI] [PubMed] [Google Scholar]
- Weeks D. P., Collis P., Gealt M. A. Control of induction of tubulin synthesis in Chlamydomonas reinhardi. Nature. 1977 Aug 18;268(5621):667–668. doi: 10.1038/268667a0. [DOI] [PubMed] [Google Scholar]
- White B. A., Bancroft F. C. Cytoplasmic dot hybridization. Simple analysis of relative mRNA levels in multiple small cell or tissue samples. J Biol Chem. 1982 Aug 10;257(15):8569–8572. [PubMed] [Google Scholar]
- Wilhelm M. L., Toublan B., Jalouzot R., Wilhelm F. X. Histone H4 gene is transcribed in S phase but also late in G(2) phase in Physarum polycephalum. EMBO J. 1984 Nov;3(11):2659–2662. doi: 10.1002/j.1460-2075.1984.tb02190.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilhelm M. L., Wilhelm F. X. A transposon-like DNA fragment interrupts a Physarum polycephalum histone H4 gene. FEBS Lett. 1984 Mar 26;168(2):249–254. doi: 10.1016/0014-5793(84)80256-2. [DOI] [PubMed] [Google Scholar]
- Wright M., Tollon Y. Regulation of thymidine kinase synthesis during the cell cycle of Physarum polycephalum by the heat-sensitive system which triggers mitosis and S phase. Exp Cell Res. 1979 Sep;122(2):273–279. doi: 10.1016/0014-4827(79)90304-5. [DOI] [PubMed] [Google Scholar]
