Zygotic genome activation(ZGA),the second step of maternal to zygotic transition(MZT),occurs at about mid-blastula transition(MBT)in zebrafish.One of many existing hypotheses on how this process happens is chromatin remodeling.Genome-wide demethylation and remethylation occur after fertilization,up to blastula stages,and DNA methylation levels are strongly correlated with transcriptional potentials.There must exist some general maternal factors regulating ZGA by demethylating or methylating DNA at the genome level.So we carry out an ENU-mediated forward genetic screen to identify those mutations that affect the DNA methylation level.For saving time,a two-generation-screen for dominant mutants was adopted.Out of about 3,000 F1 females,two mutants have been figured out with elevated DNA methylation in all of their embryos at the MZT stages.We are now mapping the affected genes and to unveil their implication in ZGA.