Attenuation of Forkhead signaling by the retinal determination factor DACH1

J Zhou, C Wang, Z Wang, W Dampier… - Proceedings of the …, 2010 - National Acad Sciences
J Zhou, C Wang, Z Wang, W Dampier, K Wu, MC Casimiro, I Chepelev, VM Popov, A Quong…
Proceedings of the National Academy of Sciences, 2010National Acad Sciences
The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive
growth factor mutant ellipse, encodes a key component of the retinal determination gene
network that governs cell fate. Herein, cyclic amplification and selection of targets identified
a DACH1 DNA-binding sequence that resembles the FOX (F orkhead b ox–containing
protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites
identified gene clusters populating cellular pathways associated with the cell cycle and …
The Drosophila Dachshund (Dac) gene, cloned as a dominant inhibitor of the hyperactive growth factor mutant ellipse, encodes a key component of the retinal determination gene network that governs cell fate. Herein, cyclic amplification and selection of targets identified a DACH1 DNA-binding sequence that resembles the FOX (Forkhead box–containing protein) binding site. Genome-wide in silico promoter analysis of DACH1 binding sites identified gene clusters populating cellular pathways associated with the cell cycle and growth factor signaling. ChIP coupled with high-throughput sequencing mapped DACH1 binding sites to corresponding gene clusters predicted in silico and identified as weight matrix resembling the cyclic amplification and selection of targets–defined sequence. DACH1 antagonized FOXM1 target gene expression, promoter occupancy in the context of local chromatin, and contact-independent growth. Attenuation of FOX function by the cell fate determination pathway has broad implications given the diverse role of FOX proteins in cellular biology and tumorigenesis.
National Acad Sciences