Flame retardant tetrabromobisphenol A (TBBPA) disrupts histone acetylation during zebrafish maternal-to-zygotic transition.

3,3',5.5'-Tetrabromobisphenol A (TBBPA) is a widely used brominated flame-retardant. The objective of this study is to use zebrafish as a model and determine the effects of TBBPA exposure on early embryogenesis. We initiated TBBPA exposures at 0.75 h post fertilization (hpf) and showed that TBBPA induced developmental delays during maternal-to-zygotic transition (MZT) and zygotic genome activation (ZGA). To examine the genetic basis of TBBPA-induced delays, we conducted mRNA-sequencing on embryos exposed to 0 or 40 μM TBBPA from 0.75 hpf to 2, 3.5 or 4.5 hpf. Read count data showed that while TBBPA exposures had no overall impacts on maternal or maternal-zygotic genes, collective read counts for zygotically activated genes were lower in TBBPA treatment at 4.5 hpf compared to time-matched controls, suggesting that TBBPA delays ZGA. Gene ontology assessments for both time- and stage-matched differentially expressed genes revealed TBBPA-induced inhibition of chromatin assembly- a process regulated by histone modifications. Immunostaining and in vitro experiments showed inhibition of histone H3 lysine 27 acetylation (H3K27Ac) as well as its catalyzing enzyme, p300. Finally, co-exposure with a p300 activator showed partial mitigation of effects, demonstrating that inhibition of histone acetylation drives TBBPA-induced developmental delays.