HMG-box factor SoxD/Sox15 and homeodomain-containing factor Xanf1/Hesx1 directly interact and regulate the expression of Xanf1/Hesx1 during early forebrain development in Xenopus laevis

The homeodomain-containing transcription factor Anf (also known as Rpx/Hesx1 in mammals) plays an important role during the forebrain development in vertebrates. Here we demonstrate the ability of the Xenopus laevis Anf, Xanf1/Hesx1, to directly bind SRY-related HMG-box-containing transcription factor SoxD/Sox15 and to cooperate with the latter during regulating of the expression of Xanf1/Hesx1 own gene. As we have shown by GST pull-down, EMSA and the luciferase reporter assays, Xanf1/Hesx1 and SoxD/Sox15 bind the Xanf1/Hesx1 promoter region counteracting the inhibitory effect of Xanf1/Hesx1 alone. This finding explains how Xanf1/Hesx1 could escape the repressive activity of its own protein during early patterning of the forebrain rudiment. •The homeodomain of Xanf1/Hesx1 interacts with HMG-box of Sox15/SoxD.•Xanf1/Hesx1 and Sox15/SoxD separately and in the complex associate with regulatory elements in the Xanf1 promoter.•Binding of Sox15/SoxD to the promoter of Xanf1 stabilizes Xanf1/Hesx1 expression in the anterior neuroectoderm.