Identification of candidate genomic regulatory elements involved in oral clefts

Project Summary/Abstract
Disturbances in the molecular pathways that control lip and palate development during embryogenesis
can lead to oral clefts, but knowledge of the regulatory interactions involved in modulating the expression
of genes in these pathways remains limited. Because enhancers are critical to the spatiotemporal
regulation of gene expression during embryogenesis, those that are active in craniofacial tissues during
lip and palate development are likely to control the expression of genes relevant to oral clefts. The overall
goal of the proposed research is to identify interactions between enhancers, transcription factors that
bind the enhancers, and target genes of the enhancers in lip and palate development and oral clefts. Aim
1 is to identify the subset of enhancers that drive gene expression overall in human embryonic palatal
mesenchyme cells. The transcription factors with binding site motifs that are enriched in the enhancers
will be identified, and binding of the transcription factors within the enhancers in human embryonic
palatal mesenchyme cells will be confirmed using assays of chromatin immunoprecipitation followed by
sequencing. Aim 2 is to identify enhancers that regulate transcription specifically within human embryonic
palatal mesenchyme cells, because such enhancers are more likely to be involved in craniofacial-specific
processes during development. Enhancers that can distinguish between human embryonic palatal
mesenchyme cells and other types of tissues and cells will be considered palate-specific enhancers. The
palate specificity of a subset of the enhancers will be confirmed using in vitro assays.

Grant Number: 7R03DE034666-02
NIH Institute/Center: NIH
Principal Investigator: Tonia Carter