Identification of a Hoxc8-regulated transcriptional network in mouse embryo fibroblast cells
- Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06511
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Contributed by Frank H. Ruddle, May 4, 2006
Abstract
The transcription factor, Hoxc8, is a member of the homeobox gene family that is vital for growth and differentiation. Previously, we identified 34 genes whose expression levels were changed at least 2-fold by forced expression of Hoxc8 in C57BL/6J mouse embryo fibroblast cells using a mouse 16,463-gene oligonucleotide microarray. In the present study, we used the combined power of microarray profiling, global Hoxc8 DNA-binding site analysis, and high-throughput chromatin immunoprecipitation assays to identify direct and biologically relevant targets of Hoxc8 in vivo. Here we show that 19 of the 34 responsive genes contain Hoxc8 consensus DNA-binding sequence(s) in their regulatory regions. Chromatin immunoprecipitation analysis indicated that Hoxc8-DNA interaction was detected in five of the 19 candidate genes. All of these five target genes have been implicated in oncogenesis, cell adhesion, proliferation, and apoptosis. Overall, the genes described here should aid in the understanding of global regulatory networks of Hox genes and to provide valuable insight into the molecular basis of Hoxc8 in development and carcinogenesis.
Footnotes
- ‡To whom correspondence should be addressed. E-mail: frank.ruddle{at}yale.edu
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↵*Present address: Laboratory of Molecular Biology, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892.
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↵ †Present address: Laboratory of Muscle Biology, National Institutes of Health/National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892.
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Author contributions: H.L. and F.H.R. designed research; H.L., A.H.J., and M.-S.K. performed research; H.L. analyzed data; and H.L. wrote the paper.
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Conflict of interest statement: No conflicts declared.
- Abbreviations:
- ChIP,
- chromatin immunoprecipitation;
- En,
- embryonic day n;
- WISH,
- whole-mount in situ hybridization.
Abbreviations:
- © 2006 by The National Academy of Sciences of the USA
