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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jul 01, 2008 |
| Title |
Deletion of Histone Deacetylase 3 reveals critical roles in S-phase progression and DNA damage control |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Histone deacetylases (HDAC) are enzymes that modify key residues in histones to regulate chromatin architecture, and play a vital role in cell survival, cell cycle progression, and tumorigenesis. To understand the function of Hdac3, a critical component of the N-CoR/SMRT repression complex, a conditional allele of Hdac3 was engineered. Given the vital role of HDAC3 in normal cells and in the generation and treatment of various cancers, a conditional deletion of Hdac3 was engineered in mice. The deletion of Hdac3 in the germ line yielded very early embryonic lethality. Therefore, mouse embryonic-derived fibroblasts (MEFs) containing the Hdac3 conditional allele were used to examine the function of Hdac3 in cell viability and in cell cycle control. Given the links between Hdac3 and transcriptional repression, we used oligonucleotide micro arrays to examine RNA isolated from control and Cre recombinase expressing MEFs to define the changes in gene expression upon inactivation of Hdac3. Initially, we compared RNA from Ad-Cre infected Hdac3FL/+ and Hdac3FL/- MEFs and then we extended the analysis to Hdac3FL/- MEFs expressing Cre-ER (tamoxifen responsive Cre-estrogen receptor fusion protein). When the gene expression of ethanol-treated (vehicle) and tamoxifen-treated MEFs was compared at 72 hr post-induction, 83 genes were induced and 111 genes were down-regulated at least 1.5-fold upon inactivation of Hdac3. Approximately, 48 genes were up-regulated in both Ad-Cre and tamoxifen-treated MEFs at the 72 hr time point. The majority of the affected genes were associated with signal transduction and metabolism. Overall, few of the up-regulated genes at the 72hr time point in Ad-Cre and tamoxifen-treated MEFs are associated with apoptosis or with cell cycle control. Thus, these metabolic regulatory genes may be “core” Hdac3-regulated genes, and alterations in gene expression are unlikely to trigger apoptosis.
Keywords: Conditional knock out analysis, genetic modification
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| Overall design |
Initially, we compared RNA from Ad-Cre infected Hdac3FL/+ and Hdac3FL/- MEFs. In this analysis, RNA isolated from 64hr and 72hr post Ad-Cre infection were used. We extended the analysis to Hdac3FL/- MEFs expressing Cre-ER (tamoxifen responsive Cre-estrogen receptor fusion protein). In this analysis, two different MEF preparations (repl1 and repl2), two different time points (64hr and 72hr) were used for array analysis with tamoxifen-treated MEFs. For vehicle (ethanol) treated MEFs, two different MEF preparations (repl1 and repl2), and a single timepoint (64hr) was used.
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| Contributor(s) |
Bhaskara S, Chyla BJ, amann JM, Knutson SK, Cortez D, Sun Z, Hiebert SW |
| Citation(s) |
18406327 |
| Submission date |
Jan 23, 2008 |
| Last update date |
Apr 28, 2017 |
| Contact name |
Srividya Bhaskara |
| E-mail(s) |
srividya.bhaskara@hci.utah.edu
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| Phone |
801-213-4219
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| Organization name |
University of Utah
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| Department |
University of Utah
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| Street address |
2000 circle of hope
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| City |
salt lake city |
| State/province |
Utah |
| ZIP/Postal code |
84112 |
| Country |
USA |
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| Platforms (1) |
| GPL2995 |
ABI Mouse Genome Survey Microarray |
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| Samples (10)
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| GSM258807 |
Hdac3 Floxminus MEF Ad-Cre treated for 64hr |
| GSM258809 |
Hdac3 Floxminus MEF Ad-Cre treated for 72hr |
| GSM258810 |
Hdac3 Floxplus MEF Ad-Cre treated for 64hr |
| GSM258811 |
Hdac3 Floxplus MEF Ad-Cre treated for 72hr |
| GSM258812 |
Hdac3 Floxminus ER Cre+ MEF treated with ethanol (vehicle) for 64hr replicate 1 |
| GSM258813 |
Hdac3 Floxminus ER Cre+ MEF treated with ethanol (vehicle) for 64hr replicate 2 |
| GSM258814 |
Hdac3 Floxminus ER Cre+ MEF treated with 1 micromolar tamoxifen for 64hr replicate 1 |
| GSM258815 |
Hdac3 Floxminus ER Cre+ MEF treated with 1 micromolar tamoxifen for 64hr replicate 2 |
| GSM258816 |
Hdac3 Floxminus ER Cre+ MEF treated with 1 micromolar tamoxifen for 72hr replicate 1 |
| GSM258817 |
Hdac3 Floxminus ER Cre+ MEF treated with 1 micromolar tamoxifen for 72hr replicate 2 |
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| Relations |
| BioProject |
PRJNA108437 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE10250_RAW.tar |
4.3 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
| Processed data provided as supplementary file |
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