Abstract
During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In Drosophila, the pioneer factor Zelda is known to be essential for the progression of development; still, it regulates the activation of only a small subset of genes at ZGA. However, thousands of genes do not require Zelda, suggesting that other mechanisms exist. By conducting GRO-seq, HiC and ChIP-seq in Drosophila embryos, we demonstrate that up to 65% of zygotically activated genes are enriched for the histone variant H2A.Z. H2A.Z enrichment precedes ZGA and RNA Polymerase II loading onto chromatin. In vivo knockdown of maternally contributed Domino, a histone chaperone and ATPase, reduces H2A.Z deposition at transcription start sites, causes global downregulation of housekeeping genes at ZGA, and compromises the establishment of the 3D chromatin structure. We infer that H2A.Z is essential for the de novo establishment of transcriptional programs during ZGA via chromatin reorganization.
Highlights
During embryogenesis, the genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA)
This study uncovers a role for the histone variant H2A.Z as an important regulator of gene activation and transcription during ZGA
Our results demonstrate that H2A.Z is deposited at the transcription start sites (TSS) of the zygotic genome by maternally supplied Domino, an ATPase and histone chaperone of H2A.Z
Summary
The genome shifts from transcriptionally quiescent to extensively active in a process known as Zygotic Genome Activation (ZGA). In. Drosophila, the pioneer transcription factor Zelda is required to activate hundreds of genes before and during the major wave of ZGA7,9,10. Global alterations in core histone levels for example have been shown to affect ZGA timing and transcription in several organisms such as flies, zebrafish and frogs[15,16,17] Substantial evidence in both vertebrate and invertebrate models shows that major chromatin remodeling occurs immediately before ZGA18,19. A mutation of the embryonic-specific H1 histone variant (BigH1) causes premature ZGA onset in flies and its role becomes relevant upon challenging conditions such as low temperature[21,25] Along these lines, the histone variant H3.3 is known to be essential for early development, since its incorporation in the paternal genome just after fertilization is required for the progression of development[26]. To date it remains unclear to what extent chromatin state and structure regulates ZGA
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