We have investigated the distances of the five major histone genes from their promotors in order to determine whether in human cells these genes could be transcribed as a single polycistronic transcriptional unit. By measuring the decreases of both histone protein and histone mRNA synthesis as functions of the ultraviolet light dosage, we were able to calculate the distances of the histonc genes from their promotors. The inactivation kinetics for histone genes H1 and H3 are flrst-order, indicating a single type of transcriptional unit for each gene. The dose-response kinetics for genes H2A, H2B and H4 are flrst-order with two distinct rates; 10 to 15% of the genes for each of these histones appear to be much more sensitive to ultraviolet light inactivation than are the majority. We conclude that the transcriptional units for 85 to 90% of the genes for H2A, H2 Band H4 are similar. As determined by the inhibition of protein synthesis, the inactivation coefficients for the major component of each histone are: H1, 907mm2/erg; H2A, 878mm2/erg; H2z]B, 871 mm2/erg; H3, 965 mm2/erg; and H4, 792 mm2/erg. The sensitivities of histone mRNA synthesis to irradiation were measured by translation in vitro with similar results. The calculated target sizes for the genes (in base-pairs) are: H1, 1190; H2A, 1240; H2B, 1250; H3, 1130; and H4, 1380. This similarity in target sizes for all five of the histones genes indicates that they are primarily transcribed from individual transcriptional units.
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We thank Ulrike Traub, Margot Bialdiga and Renate Seidel for expert technical assistance. We are grateful to Drs B. Alberts, B. McCarthy, P. O’Farrell and H. Varmus for critically reading the manuscript. This work was supported in part by a grant from the Deutsche Forschungsgemeinshaft to one of us (D. G.). One author (P.H.) was supported during a portion of this work by a postdoctoral fellowship from the Anna Fuller Fund, by United States Public Health Services grants CA12705 and CA19287, by training grant lT32 CA09043 awarded by the National Cancer Institute, Department of Health, Education and Welfare, and by American Cancer Society grant VC70.