Figure 2.
DNMT and HDAC inhibitors disrupt zebrafish embryogenesis and liver development. (A) Zebrafish embryos treated with VPA or 5-Aza develop small livers. VPA treatment starting at 6 hpf delayed the appearance of the liver on day 3 and resulted in 100% of the affected embryos displaying a small, ball-shaped liver. 5-Aza treatment at 1.5 hours resulted in 50% mortality (not shown). The majority of survivors (84%) display a smaller, misshapen liver. (B) Treatment of zebrafish embryos at 6 hpf with 20 μM VPA results in increased acetylated histone H3 (Ac-H3) at 5 dpf. (C) Treatment of zebrafish embryos with 5-Aza at 1.5 hpf results in a global loss of DNA methylation. The methylation sensitive (HpaII) and methylation insensitive (MspI) enzymes were used to assess changes in methylation levels in untreated and 5-Aza treated embryos. The smear in the HpaII lane of the 5-Aza treated embryos indicates increased digestion of the DNA, reflecting decreased methylation.