Abstract
In Xenopus, cells from the animal hemisphere are competent to form mesodermal tissues from the morula through to the blastula stage1. Loss of mesodermal competence at early gastrula is programmed cell-autonomously, and occurs even in single cells at the appropriate stage2. To determine the mechanism by which this occurs, we have been investigating a concomitant, global change in expression of H1 linker histone subtypes. H1 histones are usually considered to be general repressors of transcription3, but in Xenopus they are increasingly thought to have selective functions in transcriptional regulation4,5,6. Xenopus eggs and embryos at stages before the midblastula transition7 are deficient in histone H1 protein, but contain an oocyte-specific variant called histone B4 or H1M. After the midblastula transition, histone B4 is progressively substituted by three somatic histone H1 variants, and replacement is complete by early neurula8,9. Here we report that accumulation of somatic H1 protein is rate limiting for the loss of mesodermal competence. This involves selective transcriptional silencing of regulatory genes required for mesodermal differentiation pathways, like muscle, by somatic, but not maternal, H1 protein.
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Jones, E. A. & Woodland, H. R. The development of animal cap cells in Xenopus: a measure of the start of animal cap competence to form mesoderm. Development 101, 557–563 (1987).
Grainger, R. M. & Gurdon, J. B. Loss of competence in amphibian induction can take place in single nondividing cells. Proc. Natl Acad. Sci. USA 86, 1900–1904 (1989).
Paranjape, S. M., Kamakaka, R. T. & Kadonaga, J. T. Role of chromatin structure in the regulation of transcription by RNA polymerase II. Annu. Rev. Biochem. 63, 265–297 (1994).
Bouvet, P., Dimitrov, S. & Wolffe, A. P. Specific regulation of Xenopus chromosomal 5S rRNA gene transcription in vivo by histone H1. Genes Dev. 8, 1147–1159 (1994).
Kandolf, H. The H1A histone variant is an in vivo repressor of oocyte-type 5S gene transcription in Xenopus laevis embryos. Proc. Natl Acad. Sci. USA 91, 7257–7260 (1994).
Patterton, D. & Wolffe, A. P. Developmental roles for chromatin and chromosomal structure. Dev. Biol. 173, 2–13 (1996).
Newport, J. & Kirschner, M. Amajor developmental transition in early Xenopus embryos: II. control of the onset of transcription. Cell 30, 687–696 (1982).
Dworkin-Rastl, E., Kandolf, H. & Smith, R. C. The maternal histone H1 variant, H1M (B4 protein), is the predominant H1 histone in Xenopus pregastrula embryos. Dev. Biol. 161, 425–439 (1994).
Dimitrov, S., Almouzni, G., Dasso, M. & Wolffe, A. P. Chromatin transitions during early Xenopus embryogenesis: changes in histone H4 acetylation and in linker histone type. Dev. Biol. 160, 214–227 (1993).
Smith, J. C. Mesoderm-inducing factors and mesodermal patterning. Curr. Opin. Cell Biol. 7, 856–861 (1995).
Symes, K. & Smith, J. C. Gastrulation movements provide an early marker of mesoderm induction in Xenopus laevis. Development 101, 339–349 (1987).
Nieuwkoop, P. D. & Faber, J. Normal table of Xenopus laevis (Daudin) (North-Holland, Amsterdam, (1967)).
Rudnicki, M. A. et al. MyoD or Myf-5 is required for the formation of skeletal muscle. Cell 75, 1351–1359 (1993).
Hopwood, N. D., Pluck, A. & Gurdon, J. B. MyoD expression in the forming somites is an early response to mesoderm induction in Xenopus embryos. EMBO J. 8, 3409–3417 (1989).
Rupp, R. A. W. & Weintraub, H. Ubiquitous MyoD transcription at the midblastula transition precedes induction-dependent MyoD expression in presumptive mesoderm of X. laevis. Cell 65, 927–937 (1991).
Smith, J. C., Price, B. M. J., Green, J. B. A., Weigel, D. & Hermann, B. G. Expression of a Xenopus homolog of Brachyury (T) is an immediate-early response to mesoderm induction. Cell 67, 79–87 (1991).
Köster, M. et al. Bone morphogenetic protein 4 (BMP-4), a member of the TGF-β family, in early embryos of Xenopus laevis: analysis of mesoderm inducing activity. Mech. Dev. 33, 191–200 (1991).
Christian, J. L., McMahon, J. A., McMahon, A. P. & Moon, R. T. Xwnt-8, a Xenopus Wnt-1/int-1-related gene responsive to mesoderm-inducing growth factors, may play a role in ventral mesodermal patterning during embryogenesis. Development 111, 1045–1055 (1991).
Pevny, L. et al. Erythroid differentiation in chimaeric mice blocked by a targeted mutation in the gene for transcription factor GATA-1. Nature 349, 257–260 (1991).
Svaren, J. & Hörz, W. Regulation of gene expression by nucleosomes. Curr. Opin. Genet. Dev. 6, 164–170 (1996).
Hartzog, G. A. & Winston, F. Nucleosomes and transcription: recent lessons from genetics. Curr. Opin. Genet. 7, 192–198 (1997).
Krieg, P. & Melton, D. A. Developmental regulation of a gastrula-specific gene injected into fertilized Xenopus eggs. EMBO J. 4, 3463–3471 (1985).
Tsuda, T., Hamamori, Y., Yamashita, T., Fukumoto, Y. & Takai, Y. Involvement of three intracellular messenger systems, protein kinase C, calcium ion and cyclic AMP, in the regulation of c-fos gene expression in Swiss 3T3 cells. FEBS Lett. 208, 39–42 (1986).
Frank, D. & Harland, R. M. Transient expression of XMyoD in non-somitic mesoderm of Xenopus gastrulate. Development 113, 1387–1393 (1991).
Dale, L. & Slack, J. M. W. Fate map for the 32-cell stage of Xenopus laevis. Development 99, 527–551 (1987).
Rupp, R. A. W., Snider, L. & Weintraub, H. Xenopus embryos regulate the nuclear localization of XMyoD. Genes Dev. 8, 1311–1323 (1994).
Steinbeisser, H., Fainsod, A., Niehrs, C., Sasai, Y. & De Robertis, E. M. The role of gsc and BMP-4 in dorsal-ventral patterning of the marginal zone in Xenopus: a loss-of-function study using antisense RNA. EMBO J. 14, 5230–5243 (1995).
Sokol, S., Wong, G. G. & Melton, D. A. Amouse macrophage factor induces head structures and organizes a body axis in Xenopus. Science 249, 561–564 (1990).
Bader, D., Masaki, T. & Fischman, D. A. Immunochemical analysis of myosin heavy chain during avian myogenesis in vivo and in vitro. J. Cell Biol. 95, 763–770 (1982).
Acknowledgements
We thank M. Leu for help with RT–PCR; S. Dimitrov and R. Smith for B4/H1 antisera; S. Wendler for PCR primers; and C. Dreyer and H. Steinbeisser for comments.
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Steinbach, O., Wolffe, A. & Rupp, R. Somatic linker histones cause loss of mesodermal competence in Xenopus. Nature 389, 395–399 (1997). https://doi.org/10.1038/38755
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DOI: https://doi.org/10.1038/38755
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