Histone mRNA concentrations are regulated at the level of transcription and mRNA degradation.

The levels of histone mRNA are rapidly reduced after treatment of cultured cells with hydroxyurea or cytosine arabinonucleoside. The histone mRNA for the replicative histone variants is destroyed rapidly, with a half-life of 10-15 min. The levels of mRNA coding for the replacement histone variant H3.3 were unchanged after treatment with DNA synthesis inhibitors. In addition to the rapid destruction of histone mRNA, there was a reduction to 1/5th in the rate of transcription of the histone genes. Lymphoma cells (S49) arrested in G1 by cyclic AMP produce and contain significant levels of histone mRNA. Hydroxyurea reduces the rate of transcription and the levels of histone mRNA in the G1-arrested cells.