biostudies-literatureCollier ANCRR NIH HHSNCI NIH HHSNIAMS NIH HHS188-196https://www.ebi.ac.uk/biostudies/studies/S-EPMC9202145biostudies-literatureUnknown606(7912)Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from regional mesoderm^1-6. 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 gene^7-9, 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 GATA3NatureGibbin mesodermal regulation patterns epithelial development.PMC9202145R01 AR054780S10 RR025518P30 CA124435R01 AR073170F32 AR074221Oro AETorkelson JZhen HCollier APatel TPattison JMcCarthy KLiu AGaddam SGhanim HfalseGibbin mesodermal regulation patterns epithelial development.Proper ectodermal patterning during human development requires previously identified transcription factors such as GATA3 and p63, as well as positional signalling from regional mesoderm^1-6. 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 gene^7-9, 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 GATA32022-01-01T00:00:00Z2022 Jun2026-05-09T14:12:58.97Z2025-04-06T14:07:17.237ZS-EPMC92021453558523710.1038/s41586-022-04727-9