Adam13 interacts with large protein complexes to regulate histone modification and gene expression

Cranial neural crest (CNC) cells are a key stem cell like tissue that contribute to most of the facial structures in vertebrates. A disintegrin and metalloproteinase (ADAM) family of proteins is essential for the induction and migration of the CNC. We have shown that Adam13 interacts with the transcription factor Arid3a to regulate gene expression; we show that Adam13 modulates histone modifications in the CNC and that Arid3a binding to the tfap2α promoter is dependent on the presence of Adam13. These associations promote the expression of a certain tfap2α variant expressed in the CNC that uniquely activates the expression of genes critical to CNC migration. Furthermore, we show that both Adam13 and human ADAM9 are associated with proteins involved in histone modifications and RNA splicing (a function critically affected by the loss of Adam13). Thus, we propose that ADAMs may act as extracellular sensors to modulate chromatin availability, leading to changes in gene expression and splicing.