View Program - 63rd Annual Drosophila Research Conference

The zygotic genome is mostly unstructured and quiescent, so embryos are maternally loaded with proteins and RNAs that control early development. However, at some point, the zygotic genome must activate and begin transcribing necessary genes to assist in the early cellular divisions, a process known as zygotic genome activation (ZGA). The initial organization and transcriptional activation of the zygotic genome is facilitated by pioneering transcription factors that are able to bind and open regions of nucleosome-bound DNA. The histone proteins, which are critical to chromatin organization and regulation of the cell cycle, are some of the earliest expressed proteins from the zygotic genome. The five canonical, replication-dependent histone genes cluster in the genomes of metazoans, forming histone loci. A suite of factors known as the Histone Locus Body (HLB) act upon histone loci and regulate histone expression. The genome of Drosophila melanogaster carries a single histone locus of 107 tandem copies of the 5kb histone gene array. It remains unclear how the histone locus is activated and the HLB is established and maintained. The pioneer factor Zelda, a maternally deposited, zinc-finger protein, is the “master regulator” of ZGA and binds across the genome to “TAGteam” sites, opening chromatin and marking surrounding regions for activation and transcription. We discovered the Zelda targets TAGteam sites in the histone locus as early as embryonic nuclear cycle 8. A histone array transgene in which the TAGteam sites are ablated fails to attract HLB factors suggesting that Zelda is necessary for HLB formation in the early embryo and is involved in activating zygotic histone gene expression. In the future, we will restore Zelda to the transgenic histone array using dCas9 and assay rescue of HLB formation. Overall, our results indicate that one indirect mechanism through which pioneer factors remodel the zygotic genome is through zygotic histone gene expression.

Developmental regulation of histone genes by pioneer factor Zelda