FOXK1/2 are transcription factors that belong to the forkhead family of the winged-helix DNA-binding domain. They can function as both transcriptional activators and repressors in metazoans. Here we demonstrate that FOXK proteins bind methylated DNA in vivo and in vitro thus further elaborating on their potential function as transcriptional repressors. Triple morpholino knockdown of zebrafish foxk1/2/2-1 leads to widespread transcriptomic changes chiefly related to cell cycle control and mitosis. Whereas morpholino depletion of foxk1/2/2-1 is embryonically lethal, this knockdown can be partially rescued by the human isoform of foxk1, further emphasizing the pan-vertebrate importance of FOXK-mediated transcriptional regulation. To determine the binding sites of FOXK1/2 in the genome and their methylation state in vivo, we are employing CRISPR/Cas9 technologies to add the HA-tag to endogenous foxk1/2 loci, which will facilitate future ChIP-seq and bisulfite ChIP-seq approaches. Overall, our work demonstrates that FOXK proteins are essential multifaceted transcriptional regulators that might exert their function through DNA methylation binding.