E-GEOD-50951 - EZH2-mediated H3K27 trimethylation mediates neurodegeneration in ataxia-telangiectasia

Released on 25 October 2013, last updated on 3 June 2014
Mus musculus
Samples (4)
Array (1)
Protocols (5)
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. Two samples each were run of brain total RNA from Atm+/+ and Atm-/- mice.
Experiment type
transcription profiling by array 
Ronald P. Hart <rhart@rci.rutgers.edu>, Jiali Li, Karl Herrup, Ronald P Hart
Investigation descriptionE-GEOD-50951.idf.txt
Sample and data relationshipE-GEOD-50951.sdrf.txt
Processed data (1)E-GEOD-50951.processed.1.zip
Additional data (1)E-GEOD-50951.additional.1.zip
Array designA-MEXP-1175.adf.txt