Cell-cycle-dependent repression of histone gene transcription by histone H4

In all eukaryotes DNA replication is coupled to histone synthesis to coordinate chromatin packaging of the genome. Canonical histone genes coalesce in the nucleus into the Histone Locus Body (HLB), where gene transcription and 3' mRNA processing occurs. Both histone gene transcription and mRNA stability are reduced when DNA replication is inhibited, implying that the Histone Locus Body senses the rate of DNA synthesis. In Drosophila melanogaster, the S-phase-induced histone genes are repeated in an ~100 copy repeat unit array, whereas in humans, these histone genes are scattered. In both organisms these genes coalesce into Histone Locus Bodies. Overall design: We used a transgenic histone gene reporter and RNAi in Drosophila to identify canonical H4 histone as a unique repressor of histone synthesis during the G2 phase in germline primary spermatocytes.