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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Aug 01, 2019 |
| Title |
Tamoxifen induction of Cre recombinase does not cause long lasting or sexually divergent responses in the CNS epigenome or transcriptome: implications for the design of aging studies. |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
The systemic delivery of tamoxifen (Tam) to activate inducible CreERT2-loxP transgenic mouse systems is now widely used in neuroscience studies. This critical technological advancement allows temporal control of DNA-cre recombination, avoidance of embryonically lethal phenotypes, and minimization of residual cell labeling encountered in constitutively active drivers. Despite its advantages, the use of Tam has the potential to cause long-lasting, uncharacterized side effects on the transcriptome and epigenome in the CNS, given its mixed estrogen receptor (ER) agonist/antagonist actions. With the welcome focus on including both sexes in biomedical studies and efforts to understand sex differences, Tam administration could also cause sexually divergent responses that would confound studies. To examine these issues, epigenetic and transcriptomic profiles were compared in C57BL/6J female and male hippocampus, cortex, and retina 1 month after a five- day Tam treatment typical for cre induction, or vehicle control (sunflower seed oil). Cytosine methylation and hydroxymethylation levels, in both CG and non-CG contexts, were unchanged as determined by oxidative bisulfite sequencing. Long-lasting Tam transcriptomic effects were also not evident/minimal. Furthermore, there is no evidence of sexually divergent responses with Tam administration and Tam did not alter sex differences evident in controls. Combined with recently reported data that Tam alone does not cause long-lasting changes in behavior and neurogenesis, our findings provide confidence that Tam can be used as a cre-recombinase inducer without introducing significant confounds in transcriptomic and epigenomic neuroscience studies, particularly those focused on genomic and transcriptomic aspects of the aging brain.
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| Overall design |
Examination of the effect of tamoxifen administration on DNA methylation and hydroxymethylation in the retina, cortex, and hippocampus of mouse by Whole Genome Oxidative Bisulfite-Seq.
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| Contributor(s) |
Chucair-Elliott AJ, Ocanas SR, Stanford DR, Hadad N, Wronowski B, Otalora L, Stout MB, Freeman WM |
| Citation(s) |
31493147 |
| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| I01 BX003906 |
Dynamics of the brain epigenome with aging |
OKLAHOMA CITY VA MEDICAL CENTER |
WILLARD M FREEMAN |
| P30 AG050911 |
Targeted DNA Methylation and Mitochondrial Heteroplasmy Core |
University of Oklahoma Health Sciences Center |
WILLARD M FREEMAN |
| R01 AG059430 |
Sex divergence and cell specificity of age-related hippocampal DNA modifications |
University of Oklahoma Health Sciences Center |
WILLARD M FREEMAN |
| R21 AG062894 |
Does Dietary Restriction Alter Stem Cell Function Through An Epigenetic Mechanism? |
University of Oklahoma Health Sciences Center |
WILLARD M FREEMAN |
| R56 AG059430 |
Sex divergence and cell specificity of age-related hippocampal DNA modifications |
University of Oklahoma Health Sciences Center |
WILLARD M FREEMAN |
| F31 AG064861 |
Epigenetic regulation of sexually divergent neuroinflammation with brain aging and Alzheimer's disease |
University of Oklahoma Health Sciences Center |
Sarah Renee Ocanas |
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| Submission date |
Jul 31, 2019 |
| Last update date |
Nov 06, 2019 |
| Contact name |
Michael Stout |
| E-mail(s) |
michael-stout@omrf.org
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| Organization name |
Oklahoma Medical Research Foundation
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| Department |
Aging and Metabolism
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| Street address |
825 N.E. 13th Street
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| City |
Oklahoma City |
| State/province |
OK |
| ZIP/Postal code |
73104 |
| Country |
USA |
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| Platforms (1) |
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| Samples (72)
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| Relations |
| BioProject |
PRJNA557725 |
| SRA |
SRP217005 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE135208_RAW.tar |
2.2 Gb |
(http)(custom) |
TAR (of COV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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