Aberrant expression pattern of replication-dependent histone h3 subtype genes in human tumor cell lines.

We have determined the expression pattern of all 11 human replication-dependent histone H3 genes in three fetal human tissues (bladder, liver, and lung) and in eight human cell lines by RNase protection assay. In the fetal human tissues, all 11 genes were expressed to a varied extent. However, the relative contribution of each gene to the total replication-dependent histone H3 mRNA was rather similar in every tissue type. The expression pattern in the fibroblast cell line IMR 90 was similar to the expression pattern in the three fetal tissues. In contrast, the expression patterns varied substantially in seven tumor cell lines: some genes were not expressed at all, and others were expressed much less than in the fetal tissues or the fibroblast cell line. This aberrant expression was different in each of the cell lines tested. In a transient reporter gene assay using the promoters of 6 of the 11 genes, however, the relative activities of the promoters were similar in all cell lines. This indicates that the aberrant expression pattern in the different tumor cell lines is not due to a differential availability of transcription factors. We conclude that the varied expression pattern of the replication-dependent histone H3 genes in the examined human tumor cell lines is most probably due to epigenetic factors, such as the chromosomal context in the different cell lines.