Differential expression of individual members of the histone multigene family due to sequences in the 5' and 3' regions of the genes.

Histone proteins are encoded by a multigene family. The H3.2(614) and H2a(614) genes are present as single copies which are expressed at high levels, accounting for 30 to 40% of the H3 and H2a mRNAs, respectively, in different types of mouse cells. The other genes which have been isolated each contribute only a very small amount to the total type-specific mRNA pool. We demonstrate here that the differences in the level of expression of these genes are partly due to differences in their transcription rates. To investigate the sequences responsible for these differences in expression among the members of each family, we carried out DNA-mediated gene transfer experiments with both intact and chimeric histone genes. The 5' region of a highly expressed gene [H3.2(614) or H2a(614)] was attached to the 3' region of a histone gene which was expressed at low levels (H3-221 or H2a-291) and vice versa. The results show that sequences in both the 5' and 3' regions of the H3.2(614) and H2a(614) genes contribute to their high level of mRNA production by two independent mechanisms. The effect of the 3' sequences on mRNA accumulation has been narrowed to a 65-base-pair region including the 3'-terminal palindrome and downstream signal implicated in mRNA processing.