The genomic location and S-phase timing of origins of DNA replication change during multicellular development. Chromatin modifications influence differences in origin location and timing among different cells, but how is DNA replication coordinated with development programmes? Brian Calvi and colleagues have been examining developmental gene amplification in Drosophila ovarian follicle cells (p. 3880) and now report that the histone acetyltransferase (HAT) Chameau binds to amplicon origins and is partially required for their function. Unlike its human orthologue HBO1, however, Chameau is not absolutely required for gene amplification or genomic replication. The HAT CBP (Nejire) also binds to amplicon origins and is partially required for amplification, report the researchers, and Chameau and CBP collaborate in origin replication. Finally, Chameau and CBP globally regulate the developmental transition of follicle cells from endocycling to gene amplification. Thus, multiple HATs coordinate amplicon origin activity with follicle cell differentiation, and the researchers propose that origin regulation by multiple chromatin modifiers may be a general theme in development.