Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling

Hans Martin Herz, Marc Alard Morgan, Xin Gao, Jessica Jackson, Ryan Rickels, Selene K. Swanson, Laurence Florens, Michael P. Washburn, Joel C. Eissenberg, Ali Shilatifard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

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 languageEnglish (US)
Pages (from-to)1065-1070
Number of pages6
JournalScience
Volume345
Issue number6200
DOIs
StatePublished - Aug 29 2014

ASJC Scopus subject areas

  • General

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