Coordinated expression of replication-dependent histone genes from multiple loci promotes histone homeostasis in Drosophila

Production of large amounts of histone proteins during S phase is critical for properchromatin formation and genome integrity. This process is achieved in part by thepresence of multiple copies of replication dependent (RD) histone genes that occurin one or more clusters in metazoan genomes. In addition, RD histone gene clustersare associated with a specialized nuclear body, the histone locus body (HLB), whichfacilitates efficient transcription and 3' end-processing of RD histone mRNA. How allfive RD histone genes within these clusters are coordinately regulated such thatneither too few nor too many histones are produced, a process we refer to ashistone homeostasis, is not understood. Here, we explored the mechanisms ofcoordinate regulation between multiple RD histone loci in Drosophila melanogasterand Drosophila virilis. We provide evidence for functional competition betweenendogenous and ectopic transgenic histone arrays located at different chromosomallocations in D. melanogaster that helps maintain proper histone mRNA levels.Consistent with this model, in both species we found that individual histone genearrays can independently assemble an HLB that results in activehistone transcription. Our findings suggest a role for HLB assembly in coordinatingRD histone gene expression to maintain histone homeostasis.