The Notch signaling pathway controls cellular interactions important for the specification of a variety of fates in both invertebrates and vertebrates. Key players in the Notch pathway are the TLE genes (for transducin-like enhancer of split, also designated ESG for enhancer of split groucho), which are human homologs of the Drosophila groucho gene. Groucho is a transcriptional repressor that plays a key role in neurogenesis, segmentation and sex determination. TLEs associate with chromatin in live cells and specifically with Histone H3, but not with other core histones. Expression of the TLE genes, TLE1, TLE2, TLE3 and TLE4, correlate with immature epithelial cells that are progressing toward a terminally differentiated state, suggesting a role during epithelial differentiation. TLE1, TLE2 and TLE3 have elevated expression in cervical squamous metaplasias and carcinomas, while TLE4 is most highly expressed in the brain, particularly in the caudate nucleus. TLE1 and TLE4 contain SP and WD40 domains, through which TLE1 binds AML1 to inhibit AML1-induced transactivation of the CSF1 receptor. In early stages of cell differentiation, TLE1 is upregulated, and TLE2 and TLE4 are downregulated. In later stages, TLE2 and TLE4 are upregulated, and expression of TLE1 decreases.