Histone locus regulation by the <i>Drosophila</i> dosage compensation adaptor protein CLAMP

Abstract

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 <i>cis</i> and <i>trans</i> factors that target HLB components to histone genes remained unknown. Here we report that conserved GA repeat <i>cis</i> elements within the bidirectional <i>histone3-histone4</i> promoter direct HLB formation in <i>Drosophila</i> In addition, the CLAMP (chromatin-linked adaptor for male-specific lethal [MSL] proteins) zinc finger protein binds these GA repeat motifs, increases chromatin accessibility, enhances histone gene transcription, and promotes HLB formation. We demonstrated previously 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.