Abstract
Nuclear histone acetyltransferase is found to be inhibited by various nucleic acids and components. Of the adenosine phosphates, the order of inhibitory potency is ATP>ADP>AMP. Among the nucleoside triphosphates, GTP seems to be the best inhibitor, followed by ATP, CTP, and UTP. Deoxymononucleotides have the same order of inhibition potential as their ribonucleotide counterparts, with inhibition constants in the low millimolar range. Oligonucleotides and polynucleotides are much better inhibitors than mononucleotides. The inhibition constants of the DNA molecules are size dependent. Molecules larger than 40 base pairs have inhibition constants less than 18 µg/ml, whereas molecules with decreasing numbers of base pairs have increasing magnitudes of inhibition constants. However, acetyltransferase has a lower affinity for free DNA molecules than for DNA · histone complexes as revealed by its interaction with DNA-Sepharose and histone · DNA-Sepharose columns. Furthermore, native chromatin depleted of endogenous histone acetyltransferase activity shows no inhibitory effect on the enzyme. Yet heated chromatin not only loses substrate activity but also becomes an inhibitor for the enzyme. Since unmodified sea urchin sperm chromatin has been shown to be a potent acetyltransferase inhibitor, it seems possible that DNA · histone complexes may be the true inhibitory species and that the conformational states of such complexes may serve as a regulatory mechanism in the control of the enzyme activity.
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References
Alberts, B. M., Worcel, A., and Weintraub, H. (1977). On the biological implications of chromatin structure. In Bradbury, E. M., and Javaherian, K. (eds.),The Organization and Expression of the Eukaryotic Genome Academic Press, New York, pp. 165–191.
Allegra, P., Sterner, R., Clayton, and Allfrey, V. G. (1987). Affinity chromatographic purification of nucleosomes containing transcriptionally active DNA sequences.J. Mol. Biol. 196379.
Allfrey, V. G. (1977). Postsynthetic modifications of histone structures. In Li, H. J., and Eckhardt, R. A. (eds.),Chromatin and Chromosome Structure Academic Press, New York, pp. 167–192.
Allfrey, V. G., Faulkner, R., and Mirsky, A. E. (1964). Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis.Proc. Natl. Acad. Sci. USA 51786.
Belikoff, E., Wong, L.-J., and Alberts, B. M. (1980). Extensive purification of histone acetylase A, the major histone N-acetyltransferase activity detected in mammalian cell nuclei.J. Biol. Chem. 25511448.
Bonner, J., Chalkley, G. R., Dahmus, M., Fambrough, D., Fujimura, S., Huang, R.-C. C., Huberman, J., Jensen, R., Marushige, K., Ohlembusch, H., Olivera, B., and Widholm, J. (1968). Isolation and characterization of chromosomal nucleoprotein.Methods Enzymol. XIIB3–65.
Cousens, L. S., Gallwitz, D., and Alberts, B. M. (1979). Different accessibilities in chromatin to histone acetylase.J. Biol. Chem. 2541716.
Csordas, A. (1990). On the biological role of histone acetylation.Biochem. J. 26523.
Davie, J. R., and Candido, E. P. M. (1978). Acetylated histone H4 is preferentially associated with template-active chromatin.Proc. Natl. Acad. Sci. USA 753574.
Delange, R. J., and Smith, E. L. (1975). Histone function and evolution as viewed by sequence studies.Ciba Found. Symp. 2859.
Dixon, G. H., Candido, E. P. M., Honda, B. M., Louie, A. J., MacLeod, A. R., and Sung, M. T. (1975). Biological roles of postsynthetic modifications of basic nuclear proteins.Ciba Found. Symp. 28229.
Easton, D., and Chalkley, R. (1972). High resolution electrophoretic analysis of the histones from embryos and sperm of Arbacia punctulata.Exp. Cell Res. 72502.
Felsenfeld, G. (1978). Chromatin.Nature 271115.
Fukushima, M., Ota, K., Fujimoto, D., and Horiuchi, K. (1980). Nucleosome-histone acetyltransferase from rat liver chromatin.Biochem. Biophys. Res. Commun. 921415.
Garcea, R. L., and Alberts, B. M. (1980). Comparative studies of histone acetylation in nucleosomes, nuclei and intact cell.J. Biol. Chem. 25511454.
Gould, H., and Matthews, H. R. (1976). Separation methods for nucleic acids and oligonucleotides. In Work, T. S., and Work, E. (eds.),Laboratory Techniques in Biochemistry and Molecular Biology North-Holland, Amsterdam, pp. 419–451.
Hebbes, T., Thorne, A. W., and Crane-Robinson, C. (1988). A direct link between core histone acetylation and transcriptionally active chromatin.EMBO J. 71395.
Igo-Kemenes, T., Horz, W., and Zachau, H. G. (1982). Chromatin.Annu. Rev. Biochem. 5189.
Jackson, V., Shires, A., Chalkley, R., and Granner, D. K. (1975). Studies on highly metabolically active acetylation and phosphorylation of histone.J. Biol. Chem. 2504856.
Kelner, D. N., and McCarty, K. S., Sr. (1984). Porcine liver nuclear histone acetyltransferase.J. Biol. Chem. 2593413.
Kornberg, R. (1977). Structure of chromatin.Annu. Rev. Biochem. 46931.
Marzluff, W. F., Jr., Murphy, E. C., Jr., and Jiang, R.-C. (1973). Transcription of ribonucleic acid in isolated mouse myeloma nuclei.Biochemistry 123440.
Palter, K. B., and Alberts, B. M. (1979). The use of DNA-cellulose for analyzing histone-DNA interactions.J. Biol. Chem. 25411160.
Sharpe, D. J., and Wong, L.-J. C. (1987). Nuclear histone acetyltransferase: Inactivation by group specific reagents.Fed. Proc. 461977.
Simpson, R. T. (1978). Structure of chromatin containing extensively acetylated H3 and H4.Cell 13691.
Vidali, G., Boffa, L. C., Bradbury, E. M., and Allfrey, V. G. (1978). Butyrate suppression of histone deacetylation leads to accumulation of multiacetylated forms of histone H3 and H4 and increased DNase I sensitivity of the associated DNA sequences.Proc. Natl. Acad. Sci. USA 752239.
Wong, L.-J. C. (1980). Effect of sea urchin sperm chromatin on histone acetylation.Biochem. Biophys. Res. Commun. 971362.
Wong, L.-J. C., and Alberts, B. M. (1977). Studies on histone acetylation.Fed. Proc. 36784.
Wong, L.-J. C., and Wong, S. S. (1983). Kinetic mechanism of the reaction catalyzed by nuclear histone acetyltransferase from calf thymus.Biochemistry 224637.
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Wong, LJ.C., Sharpe, D.J. Regulation of nuclear histone acetyltransferase by nucleic acids, histone · DNA complex, and chromatin. Biochem Genet 29, 13–28 (1991). https://doi.org/10.1007/BF00578236
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DOI: https://doi.org/10.1007/BF00578236