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| Status |
Public on Oct 25, 2013 |
| Title |
EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The symptoms of ataxia-telangiectasia (A-T) include a progressive neurodegeneration caused by ATM protein deficiency. We previously found that nuclear accumulation of histone deacetylase-4, HDAC4, contributes to this degeneration; we now report that increased histone H3K27 trimethylation (H3K27me3) mediated by polycomb repressive complex 2 (PRC2) also plays an important role in the A-T phenotype. Enhancer of zeste homolog 2 (EZH2), a core catalytic component of PRC2, is identified as a new ATM kinase target, and its S734 phosphorylation reduces protein stability. Thus, PRC2 formation is elevated along with H3K27me3in ATM deficiency. ChIP-sequencing shows a significant increase in H3K27me3 ‘marks’ and a dramatic shift in their location. The change of H3K27me3 chromatin-binding pattern is directly related to cell cycle re-entry and cell death of ATM-deficient neurons. Lentiviral knockdown of EZH2 rescues Purkinje cell degeneration and behavioral abnormalities in Atm / mice, demonstrating that EZH2-mediated H3K27me3 is another key factor in A-T neurodegeneration.
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| Overall design |
Two samples each were run of brain total RNA from Atm+/+ and Atm-/- mice.
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| Contributor(s) |
Li J, Hart RP, Herrup K |
| Citation(s) |
24162653, 27538496 |
| Submission date |
Sep 17, 2013 |
| Last update date |
Mar 30, 2020 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
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| Phone |
848-445-1783
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| Organization name |
Rutgers University
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| Department |
Cell Biology & Neuroscience
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| Street address |
604 Allison Rd Rm B430
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| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL6887 |
Illumina MouseWG-6 v2.0 expression beadchip |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA219417 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50951_RAW.tar |
15.8 Mb |
(http)(custom) |
TAR |
| GSE50951_non-normalized.txt.gz |
1.3 Mb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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