We have isolated and sequenced full-length cDNA clones encoding the human basally expressed H3.3 histone from a human fibroblast cDNA library. Several features of this atypical cDNA distinguish it and its gene from the well-characterized cell-cycle regulated histone genes and their RNA transcripts. The H3.3 mRNA is approximately equal to 1200 bases long, contains unusually long 5' and 3' untranslated regions, and has a 3' polyadenylylated terminus. In addition, we have isolated and characterized a cDNA clone that is a precursor to the H3.3 mRNA and contains an intervening sequence interrupting its 5' untranslated region. Hybridization of subsegments of the cDNA to human genomic DNA reveals a complex multigene family. The differences in the structures of basal and cell-cycle histone genes suggest a model to explain the differences in their expression.
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