Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMP

The conserved histone locus body (HLB) assembles prior to zygotic gene activation early during development and concentrates factors into a nuclear domain of coordinated histone gene regulation. Although HLBs form specifically at replication dependent histone loci, the cis and trans factors that target HLB components to histone genes remained unknown. Here we report that conserved GA-repeat cis elements within the bidirectional histone3-histone4 promoter direct HLB formation in Drosophila. In addition, the CLAMP zinc-finger protein binds these GA-repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We previously demonstrated that CLAMP also promotes the formation of another domain of coordinated gene regulation: the dosage-compensated male X-chromosome. Therefore, CLAMP binding to GA-repeat motifs promotes the formation of two distinct domains of coordinated gene activation located at different places in the genome. Examination of gene expression in 0-2 and 2-4 hour Drosophila embryos after clamp depletion by RNAi