Capasso O, Heintz N
Proc Natl Acad Sci U S A. 1985 Sep;82(17):5622-6. doi: 10.1073/pnas.82.17.5622.
Mouse L cells containing integrated copies of a human histone H4 gene have been obtained by cotransfection with the herpesvirus thymidine kinase gene. Nuclease S1 assays of RNA from several independent cell lines show that the expression of the introduced H4 gene is regulated during the cell cycle. One of these cell lines (line 6-8) contains more than 60 human H4 gene copies per haploid genome and does not express the endogenous mouse histone H4 mRNA. In contrast, the expression of the mouse H2a and H3 mRNAs in this cell line is not perturbed. In cell revertants that have lost the majority of the human H4 gene copies, the expression of the mouse H4 mRNA is restored, demonstrating that the mouse genes remain functional although not expressed. The rate of transcription of the histone H4 genes in clone 6-8 is at least 10-fold greater than that of the parental cell line and it is regulated during traversal of the cell cycle. These results show that the expression of mammalian histone H4 genes involves both a trans-acting transcriptional regulatory factor and an H4-specific activity. We propose that cell cycle regulation of histone gene expression may be effected through subtype-specific transcriptional regulatory proteins.
通过与疱疹病毒胸苷激酶基因共转染，已获得含有整合人类组蛋白H4基因拷贝的小鼠L细胞。对来自几个独立细胞系的RNA进行核酸酶S1分析表明，导入的H4基因的表达在细胞周期中受到调控。其中一个细胞系（6-8系）每个单倍体基因组含有60多个人类H4基因拷贝，并且不表达内源性小鼠组蛋白H4 mRNA。相比之下，该细胞系中小鼠H2a和H3 mRNA的表达未受干扰。在已丢失大部分人类H4基因拷贝的细胞回复体中，小鼠H4 mRNA的表达得以恢复，这表明小鼠基因尽管未表达但仍保持功能。克隆6-8中组蛋白H4基因的转录速率比亲代细胞系至少高10倍，并且在细胞周期进程中受到调控。这些结果表明，哺乳动物组蛋白H4基因的表达涉及一种反式作用转录调节因子和一种H4特异性活性。我们提出，组蛋白基因表达的细胞周期调控可能是通过亚型特异性转录调节蛋白实现的。
