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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Feb 21, 2020 |
| Title |
ASO-mediated RNA Suppression through Targeted Epigenetic Reprogramming of the Hdac2 Gene |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We elicited ASO-mediated knockdown of mRNAs in the nervous system by targeting the memory-repressor gene Histone deacetylase 2 (Hdac2) in vitro and in vivo. We observed that an Hdac2-targeted ASO not only triggered a reduction in mRNA levels, but also a direct transcriptional suppression of the Hdac2 gene in neurons in vitro. In further in vivo studies, we observed that a single dose of the Hdac2-targeted ASO delivered by intracerebroventricular injection into the central nervous system (CNS) achieved steady-state diminution of Hdac2 mRNA levels that lasted more than 6 months in vivo. Knockdown of this factor resulted in memory enhancement. ASO administration also caused a prolonged alteration of steady-state levels of a set of known memory-associated mRNAs and triggered secondary changes in the epigenome at sites outside of the primary target gene.
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| Overall design |
3 scrambled ASO and 3 HDAC2 ASO mice were sacrificed and at 9 timepoints (3d, 2w, 4w, 8w, 16w, 32w, 40w, 48w, 52w) after ASO injection. Cortex, hippocampus and cerebellum were analyzed for total RNA expression. expression.
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| Contributor(s) |
Greer CB, Poplawski SG, Garbett KA, McMahon RL, Kordasiewicz HB, Motley ST, Swayze EE, Ecker DJ, Goleva SB, Sanders TH, Kennedy AJ, Michael TP, Sweatt JD |
| Citation(s) |
32160709 |
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| Submission date |
Jan 07, 2019 |
| Last update date |
Mar 23, 2020 |
| Contact name |
Shane Gary Poplawski |
| E-mail(s) |
spoplaws@jcvi.org
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| Organization name |
JCVI
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| Street address |
4120 Capricorn Lane
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
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| Platforms (2) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (162)
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| Relations |
| BioProject |
PRJNA513334 |
| SRA |
SRP176459 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE124726_Table_CRB_totRNA.xlsx.gz |
19.7 Mb |
(ftp)(http) |
XLSX |
| GSE124726_Table_CTX_totRNA.xlsx.gz |
19.6 Mb |
(ftp)(http) |
XLSX |
| GSE124726_Table_HPC_totRNA.xlsx.gz |
19.1 Mb |
(ftp)(http) |
XLSX |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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