H3.3A VARIANT HISTONE MESSENGER-RNA CONTAINING AN ALPHA-GLOBIN INSERTION - MODULATED EXPRESSION DURING MOUSE GAMETOGENESIS CORRELATES WITH MEIOTIC ONSET

Replacement-variant H3.3 histones have been isolated and sequenced in different eukaryotes, but no functional H3.3A gene has been characteri zed in the mouse so far. We have cloned an H3.3A cDNA from a mouse fet al ovary library, differentially screened with testis versus somatic c DNA probes. We showed this gene contains a region homologous to the re verse and complementary alpha-globin gene, We believe such a structure could have been generated by retroposition during the evolution of bo th globin and histone gene families. The sequence coding for H3.3A is 76.6% homologous to the mouse H3.3B gene at the nucleotide level and d iffers in only one amino acid at the protein level. The high degree of homology between these genes and the H3.3 variant histones from other eukaryotes reveals the conservation of these replication-independent class of histones throughout evolution, Analysis of gene expression re veals a developmental regulation concurrent with meiotic progression, with the highest level of transcript detection coincident with meiotic onset during both oogenesis and spermatogenesis.