Zelda is dispensable for histone gene regulation.

To ensure that the embryo can package exponentially increasing amounts of DNA, replication-dependent histones are some of the earliest transcribed genes from the zygotic genome. However, how the histone genes are identified is not known. The pioneer factor CLAMP regulates the embryonic histone genes and helps establish the histone locus body, a suite of factors that controls histone mRNA biosynthesis, but CLAMP is not unique to the histone genes. Zelda collaborates with CLAMP across the genome to regulate zygotic genome activation and target early activated genes. We hypothesized that Zelda helps identify histone genes for early embryonic expression. We found that Zelda targets the histone gene locus early during embryogenesis, prior to histone gene expression. However, depletion of in the early embryo does not affect histone mRNA levels or prevent the recruitment of other factors. These results suggest the earliest events responsible for specifying the zygotic histone genes remain undiscovered.