| Autor: |
Freebern, W. J., Haggerty, C. M., Montano, I., McNutt, M. C., Collins, I., Graham, A., Chandramouli, G. V. R., Stewart, D. H., Biebuyck, H. A., Taub, D. D., Gardner, K. |
| Předmět: |
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| Zdroj: |
Pharmacogenomics Journal; 2005, Vol. 5 Issue 5, p305-323, 19p, 9 Diagrams, 2 Charts, 4 Graphs |
| Abstrakt: |
The blueprint for cellular diversity and response to environmental change is encoded in the cis-acting regulatory sequences of most genes. Deciphering this ‘cis-regulatory code’ requires multivariate data sets that examine how these regions coordinate transcription in response to diverse environmental stimuli and therapeutic treatments. We describe a transcriptional approach that profiles the activation of multiple transcriptional targets against combinatorial arrays of therapeutic and signal transducing agents. Application of this approach demonstrates how cis-element composition and promoter context combine to influence transcription downstream of mitogen-induced signaling networks. Computational dissection of these transcriptional profiles in activated T cells uncovers a novel regulatory synergy between IGF-1 and CD28 costimulation that modulates NF-κB and AP1 pathways through signaling cascades sensitive to cyclosporin A and wortmannin. This approach provides a broader view of the hierarchical signal integration governing gene expression and will facilitate a practical design of combinatorial therapeutic strategies for exploiting critical control points in transcriptional regulation.The Pharmacogenomics Journal (2005) 5, 305–323. doi:10.1038/sj.tpj.6500325; published online 26 July 2005 [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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