Catalytic-dependent and independent functions of the histone acetyltransferase CBP promote pioneer factor-mediated zygotic genome activation [RNA-seq]

Immediately after fertilization the genome is transcriptionally quiescent. Maternally encoded pioneer transcription factors reprogram the chromatin state and facilitate the transcription of the zygotic genome. In Drosophila, transcription is initiated by the pioneer factor Zelda. While Zelda-occupied sites are enriched with histone acetylation, a post-translational mark associated with active cis-regulatory regions, the functional relationship between Zelda and histone acetylation in zygotic genome activation remained unclear. We show that Zelda-mediated recruitment of the histone acetyltransferase CBP is essential for zygotic transcription and embryonic development. CBP catalytic activity is necessary for release of RNA Polymerase II (Pol II) into transcription elongation. However, CBP largely activates zygotic transcription independent of acetylation through Pol II recruitment. Neither acetylation nor CBP are required for the pioneering function of Zelda. Our data suggest that pioneer factor-mediated recruitment of CBP is a conserved mechanism required to activate zygotic transcription but that this role is separable from the function of pioneer factors in restructuring chromatin accessibility. This data set contains single-embryo RNA-seq on embryos precisely staged 15 minutes into nuclear cycle 14 during the maternal-to-zygotic transition. GFP-CBP;his2AV-RFP and GFP-CBP;nos-deGrad/+;his2AV-RFP embryos were used to quantify the effect CBP knockdown has on transcription during zygotic genome activation. To assay the catalytic function of CBP we used an optogenetic line, CRY2-CBP, to inactivate CBP mediated histone acetyltransferase with blue light treatments. CRY2-CBP;his2av-RFP were treated with blue light to inactivate CBP catalytic activity via the CRY2 optogenetic tag or left in the dark as a control to assay the function of CBP mediated acetylation during ZGA. His2AV-RFP control embryos were treated similarly and used to compare to CRY2-CBP;His2avRFP embryos.