Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63,as well as positional signalling from regional mesoderm1-6.However,the mechanism by which ectoderm and mesoderm factors act to stably pattern gene expression and lineage commitment remains unclear.Here we identify the protein Gibbin,encoded by the Xia-Gibbs AT-hook DNA-binding-motif-containing 1(AHDC1)disease gene7-9,as a key regulator of early epithelial morphogenesis.We find that enhancer-or promoter-bound Gibbin interacts with dozens of sequence-specific zinc-finger transcription factors and methyl-CpG-binding proteins to regulate the expression of mesoderm genes.The loss of Gibbin causes an increase in DNA methylation at GATA3-dependent mesodermal genes,resulting in a loss of signalling between developing dermal and epidermal cell types.
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