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| Status |
Public on Oct 24, 2005 |
| Title |
Two transactivation mechanisms are responsible for the bulk of HIF-1alpha-responsive gene expression |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The C-terminal activation domain (C-TAD) of the hypoxia-inducible transcription factors HIF-1? and HIF-2? binds the CH1 domains of the related transcriptional coactivators CREB-binding protein (CBP) and p300, an oxygen-regulated interaction thought to be highly essential for hypoxia-responsive transcription. The role of the CH1 domain in vivo is unknown, however. We created mutant mice bearing deletions in the CH1 domains (?CH1) of CBP and p300 that abrogate their interactions with the C-TAD, revealing that the CH1 domains of CBP and p300 are genetically non-redundant and indispensable for C-TAD transactivation function. Surprisingly, the CH1 domain was only required for an average of ~35-50% of global HIF-1?-responsive gene expression, whereas another HIF-transactivation mechanism that is sensitive to the histone deacetylase inhibitor trichostatin A (TSAS) accounts for ~70%. Both pathways are required for greater than 90% of the response for some target genes. Our findings suggest that a novel functional interaction between the protein acetylases CBP and p300, and deacetylases, is essential for nearly all HIF-responsive transcription.
Keywords: genetic modification, dose response
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| Overall design |
Three separate affymetrix experiments using mouse embryonic fibroblasts derived from embryos bearing the ?CH1 mutation in p300 and/or CBP and treated with hypoxia or combinations of dipyridyl (a hypoxia mimetic) and trichostatin A (a histone deacetylase inhibitor) are described (GSE3195, GSE3196 and GSE3296). Samples are not directly comparable between experiments because of differences in experiment design and Affymetrix chips used.
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| Contributor(s) |
Kasper LH, Boussouar F, Boyd K, Xu W, Biesen M, Rehg J, Baudino TA, Cleveland JL, Brindle PK |
| Citation(s) |
16237459 |
| Submission date |
Sep 16, 2005 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Paul K. Brindle |
| E-mail(s) |
paul.brindle@stjude.org
|
| Phone |
901 495 2451
|
| Organization name |
St Jude Children's Research Hospital
|
| Department |
Biochemistry
|
| Street address |
332 N Lauderdale
|
| City |
Memphis |
| State/province |
TN |
| ZIP/Postal code |
38105 |
| Country |
USA |
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| Platforms (2) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (32)
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| Relations |
| BioProject |
PRJNA93353 |
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