TFII-I and AP2α Co-Occupy the Promoters of Key Regulatory Genes Associated with Craniofacial Development

Objectives: The aim of this study is to define the candidate target genes for TFII-I and AP2α regulation in neural crest progenitor cells.

Design: The GTF2I and GTF2IRD1 genes encoding the TFII-I family of transcription factors are prime candidates for the Williams-Beuren syndrome, a complex multisystem disorder characterized by craniofacial, skeletal, and neurocognitive deficiencies. AP2α, a product of the TFAP2A gene, is a master regulator of neural crest cell lineage. Mutations in TFAP2A cause branchio-oculo-facial syndrome characterized by dysmorphic facial features and orofacial clefts. In this study, we examined the genome-wide promoter occupancy of TFII-I and AP2α in neural crest progenitor cells derived from in vitro-differentiated human embryonic stem cells.

Results: Our study revealed that TFII-I and AP2α co-occupy a selective set of genes that control the specification of neural crest cells.

Conclusions: The data suggest that TFII-I and AP2α may coordinately control the expression of genes encoding chromatin-modifying proteins, epigenetic enzymes, transcription factors, and signaling proteins.