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Attenuation of Forkhead signaling by the retinal determination factor DACH1
Journal article   Open access

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, …
Proceedings of the National Academy of Sciences - PNAS, v 107(15), pp 6864-6869
13 Apr 2010
PMID: 20351289
url
https://doi.org/10.1073/pnas.1002746107View
Published, Version of Record (VoR)Maybe Open Access (Publisher Bronze) Open

Abstract

Promoter Regions, Genetic Computational Biology - methods Retina - metabolism Humans Gene Expression Regulation Transcription Factors - metabolism Cell Lineage DNA - chemistry Eye Proteins - metabolism Forkhead Transcription Factors - metabolism Protein Binding HeLa Cells Forkhead Box Protein M1 Genome Binding Sites Chromatin - chemistry Signal Transduction
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Oncology
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