PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of jcellbiolHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
 
J Cell Biol. 1986 January 1; 102(1): 124–130.
PMCID: PMC2114035

Expression of muscle genes in heterokaryons depends on gene dosage

Abstract

We report that gene dosage, or the ratio of nuclei from two cell types fused to form a heterokaryon, affects the time course of differentiation-specific gene expression. The rate of appearance of the human muscle antigen, 5.1H11, is significantly faster in heterokaryons with equal or near-equal numbers of mouse muscle and human fibroblast nuclei than in heterokaryons with increased numbers of nuclei from either cell type. By 4 d after fusion, a high frequency of gene expression is evident at all ratios and greater than 75% of heterokaryons express the antigen even when the nonmuscle nuclei greatly outnumber the muscle nuclei. The kinetic differences observed with different nuclear ratios suggest that the concentration of putative trans-acting factors significantly influences the rate of muscle gene expression: a threshold concentration is necessary, but an excess may be inhibitory.

Full Text

The Full Text of this article is available as a PDF (862K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Blau HM, Chiu CP, Webster C. Cytoplasmic activation of human nuclear genes in stable heterocaryons. Cell. 1983 Apr;32(4):1171–1180. [PubMed]
  • Blau HM, Chiu CP, Pavlath GK, Webster C. Muscle gene expression in heterokaryons. Adv Exp Med Biol. 1985;182:231–247. [PubMed]
  • Borrelli E, Hen R, Chambon P. Adenovirus-2 E1A products repress enhancer-induced stimulation of transcription. Nature. 1984 Dec 13;312(5995):608–612. [PubMed]
  • Brown DD. The role of stable complexes that repress and activate eucaryotic genes. Cell. 1984 Jun;37(2):359–365. [PubMed]
  • Caplan AI, Ordahl CP. Irreversible gene repression model for control of development. Science. 1978 Jul 14;201(4351):120–130. [PubMed]
  • Chiu CP, Blau HM. Reprogramming cell differentiation in the absence of DNA synthesis. Cell. 1984 Jul;37(3):879–887. [PubMed]
  • Chiu CP, Blau HM. 5-Azacytidine permits gene activation in a previously noninducible cell type. Cell. 1985 Feb;40(2):417–424. [PubMed]
  • Cozzarelli NR. The mechanism of action of inhibitors of DNA synthesis. Annu Rev Biochem. 1977;46:641–668. [PubMed]
  • De Robertis EM, Gurdon JB. Gene activation in somatic nuclei after injection into amphibian oocytes. Proc Natl Acad Sci U S A. 1977 Jun;74(6):2470–2474. [PubMed]
  • GURDON JB. The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol. 1962 Dec;10:622–640. [PubMed]
  • Jacobs JP, Jones CM, Baille JP. Characteristics of a human diploid cell designated MRC-5. Nature. 1970 Jul 11;227(5254):168–170. [PubMed]
  • Lawrence JB, Coleman JR. Extinction of muscle-specific properties in somatic cell heterokaryons. Dev Biol. 1984 Feb;101(2):463–476. [PubMed]
  • Metzenberg RL, Chia W. Genetic control of phosphorus assimilation in Neurospora crassa: dose-dependent dominance and recessiveness in constitutive mutants. Genetics. 1979 Nov;93(3):625–643. [PubMed]
  • Meyer BJ, Maurer R, Ptashne M. Gene regulation at the right operator (OR) of bacteriophage lambda. II. OR1, OR2, and OR3: their roles in mediating the effects of repressor and cro. J Mol Biol. 1980 May 15;139(2):163–194. [PubMed]
  • Myers RM, Rio DC, Robbins AK, Tjian R. SV40 gene expression is modulated by the cooperative binding of T antigen to DNA. Cell. 1981 Aug;25(2):373–384. [PubMed]
  • Nadal-Ginard B. Commitment, fusion and biochemical differentiation of a myogenic cell line in the absence of DNA synthesis. Cell. 1978 Nov;15(3):855–864. [PubMed]
  • Ptashne M, Jeffrey A, Johnson AD, Maurer R, Meyer BJ, Pabo CO, Roberts TM, Sauer RT. How the lambda repressor and cro work. Cell. 1980 Jan;19(1):1–11. [PubMed]
  • Schmid V, Alder H. Isolated, mononucleated, striated muscle can undergo pluripotent transdifferentiation and form a complex regenerate. Cell. 1984 Oct;38(3):801–809. [PubMed]
  • Thompson LH, Baker RM. Isolation of mutants of cultured mammalian cells. Methods Cell Biol. 1973;6:209–281. [PubMed]
  • Tjian R. The binding site on SV40 DNA for a T antigen-related protein. Cell. 1978 Jan;13(1):165–179. [PubMed]
  • Tjian R. Protein-DNA interactions at the origin of simian virus 40 DNA replication. Cold Spring Harb Symp Quant Biol. 1979;43(Pt 2):655–661. [PubMed]
  • Walsh FS, Ritter MA. Surface antigen differentiation during human myogenesis in culture. Nature. 1981 Jan 1;289(5793):60–64. [PubMed]
  • Weiss MC. The analysis of cell differentiation by hybridization of somatic cells. Results Probl Cell Differ. 1980;11:87–92. [PubMed]
  • Wormington WM, Brown DD. Onset of 5 S RNA gene regulation during Xenopus embryogenesis. Dev Biol. 1983 Sep;99(1):248–257. [PubMed]
  • Wormington WM, Schlissel M, Brown DD. Developmental regulation of Xenopus 5S RNA genes. Cold Spring Harb Symp Quant Biol. 1983;47(Pt 2):879–884. [PubMed]
  • Wright WE. Induction of muscle genes in neural cells. J Cell Biol. 1984 Feb;98(2):427–435. [PMC free article] [PubMed]
  • Wright WE. Expression of differentiated functions in heterokaryons between skeletal myocytes, adrenal cells, fibroblasts and glial cells. Exp Cell Res. 1984 Mar;151(1):55–69. [PubMed]
  • Yaffe D, Saxel O. Serial passaging and differentiation of myogenic cells isolated from dystrophic mouse muscle. Nature. 1977 Dec 22;270(5639):725–727. [PubMed]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press