Analysis of SMAD1/5 target genes in a sea anemone reveals ZSWIM4-6 as a novel BMP signaling modulator

BMP signaling has a conserved function in patterning the dorsal-ventral body axis in Bilateria and the directive axis in anthozoan cnidarians. So far, cnidarian studies have focused on the role of different BMP signaling network components in regulating pSMAD1/5 gradient formation. Much less is known about the target genes downstream of BMP signaling. To address this, we generated a genome-wide list of direct pSMAD1/5 target genes in the anthozoan <jats:italic>Nematostella vectensis</jats:italic>, several of which were conserved in <jats:italic>Drosophila</jats:italic> and <jats:italic>Xenopus</jats:italic>. Our ChIP-seq analysis revealed that many of the regulatory molecules with documented bilaterally symmetric expression in <jats:italic>Nematostella</jats:italic> are directly controlled by BMP signaling. We identified several so far uncharacterized BMP-dependent transcription factors and signaling molecules, whose bilaterally symmetric expression may be indicative of their involvement in secondary axis patterning. One of these molecules is <jats:italic>zswim4-6</jats:italic>, which encodes a novel nuclear protein that can modulate the pSMAD1/5 gradient and potentially promote BMP-dependent gene repression.