Attenuation of Forkhead signaling by the retinal determination factor DACH1

Jie Zhou, Chenguang Wang, Zhibin Wang, Will Dampier, Kongming Wu, Mathew C. Casimiro, Iouri Chepelev, Vladimir M. Popov, Andrew Quong, Aydin Tozeren, Keji Zhao, Michael P. Lisanti, Richard G. Pestell

Research output: Contribution to journalArticlepeer-review

Abstract

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 contactindependent 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.

Original languageEnglish (US)
Pages (from-to)6864-6869
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number15
DOIs
StatePublished - Apr 13 2010
Externally publishedYes

Keywords

  • Cell fate determination
  • Dachshund homolog 1
  • Forkhead protein
  • Transcription factor
  • Tumor suppressor

ASJC Scopus subject areas

  • General

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