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Series GSE3318 Query DataSets for GSE3318
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
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
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.
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
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
Platforms (2)
GPL339 [MOE430A] Affymetrix Mouse Expression 430A Array
GPL1261 [Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array
Samples (32)
GSM67322 wildtype_normoxia
GSM67323 tri_CH1_normoxia
GSM67324 wildtype_hypoxia
BioProject PRJNA93353

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