Journal
CELL
Volume 153, Issue 5, Pages 1012-1024Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.04.032
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Funding
- Ministry of Science and Technology of China [2012CB910300]
- National Natural Science Foundation of China [30525033, 30730024]
- Fundamental Research Funds for the Central Universities of China
- National Basic Research Program of China [2012CB518700]
- MEX, Japan
- NIGMS [5R01 GM51923]
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Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes (spermatoproteasomes'') contain a spermatid/sperm-specific alpha subunit alpha 4 s/PSMA8 and/or the catalytic beta subunits of immuno-proteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.
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