The MLL/Setd1b methyltransferase is required for the Spemann's organizer gene activation in Xenopus

Abstract

Wdr5 is an essential component of SET/MLL methylase complexes that catalyze histone H3 lysine 4 trimethylation. The maternal Wnt/β-catenin signaling is necessary for the H3K4me3 deposition at organizer genes in early Xenopus embryos. However, it remains unknown whether any component of SET/MLL methylase complex is required for Wnt signaling to establish H3K4me3 at its targets during the organizer induction. Here, we provide evidence that Wdr5 is required for dorsal axis development and organizer gene activation in Xenopus. Depletion of maternal Wdr5 resulted in ventralized development, phenocopying depletion of maternal β-catenin. Depletion of maternal Wdr5 also drastically reduced the ability of β-catenin to activate organizer genes. Siamois, a direct target of maternal Wnt/β-catenin signaling, was able to reinitiate dorsal axis formation when Wdr5 was depleted. Importantly, we demonstrate that Wdr5 is required for H3K4me3 establishment at the promoter region of siamois. Moreover, we found evidence that Setd1b, a maternally provided methyltransferase, is required for organizer gene expression. Our findings indicate that Wdr5-mediated H3K4 trimethylation plays a part in the organizer formation and dorsal axis development that are controlled by the maternal Wnt/β-catenin pathway.

Keywords: H3K4 trimethylation; Organizer formation; Setd1b; Wdr5; Wnt/β-catenin signaling; Xenopus.