Abstract
Histone H3 lysine27-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas.We established a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing derepression of PRC2 target genes and developmental perturbations. Similarly, an H3K9Mmutant depletes H3K9methylation levels and suppresses position-effect variegation in various Drosophila tissues.The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M-containing nucleosomes, and its misregulation in Drosophila results in changes of H3K9 methylation levels and heterochromatic silencing defects.We have established histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin signaling pathways.
Original language | English (US) |
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Pages (from-to) | 1065-1070 |
Number of pages | 6 |
Journal | Science |
Volume | 345 |
Issue number | 6200 |
DOIs | |
State | Published - Aug 29 2014 |
ASJC Scopus subject areas
- General