Faithful cell-cycle regulation of a recombinant mouse histone H4 gene is controlled by sequences in the 3'-terminal part of the gene.

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Abstract
The expression of endogenous histone H4 genes and of a newly introduced H4 gene was analyzed in 21-Tb cells, a mouse mastocytoma cell-cycle mutant. Endogenous H4 mRNA were less abundant by a factor of 12-180 in G1-arrested than in exponentially multiplying cells. H4 transcription rates were only decreased by a factor of 3 under these conditions, as determined by in vitro elongation of nascent transcripts. Apparently, post-transcriptional control of histone mRNA levels is important, in accord with published data. A mouse H4 gene, modified by a 12-base-pair (bp) insertion in its coding sequence, was introduced into 21-Tb cells by DNA-mediated gene transfer. The levels of transcripts from this gene were regulated in parallel with those of the endogenous genes. Fusion of the SV40 early promoter to a 463-bp fragment containing the 3''-terminal half of the mouse H4 gene, including 230 bp of spacer sequences, led to the regulated expression of SV40/H4 fusion RNA. A small proportion of SV40-initiated transcripts were not processed to histone-specific 3'' ends, but extended farther through the downstream Escherichia coli galactokinase gene to a SV40 polyadenylylation site. In contrast to the short SV40/H4 RNA, the levels of these longer transcripts were not reduced in G1-arrested cells. Sequences in the 3''-terminal part of the H4 gene can regulate gene expression in the cell cycle, presumably at the post-transcriptional level, as long as they are not positioned much more distant from the terminus than normal.