Transcriptomics

Dataset Information

296

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


ABSTRACT: Histone H3 lysine27-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. Here, we establish 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 de-repression of PRC2 target genes and developmental perturbations. Similarly, a H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M nucleosomes and its overexpression in Drosophila results in loss of H3K9 methylation levels and heterochromatic silencing defects. Here we establish 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. RNA-seq of wing imaginal discs expressing either H3.3WT-FLAG-HA or H3.3K27M-FLAG-HA.

ORGANISM(S): Drosophila melanogaster  

SUBMITTER: Ali Shilatifard   Marc Morgan  Hans M Herz  Xin Gao 

PROVIDER: E-GEOD-59891 | ArrayExpress | 2014-09-02

SECONDARY ACCESSION(S): SRP045072GSE59891PRJNA256995

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

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

Herz Hans-Martin HM   Morgan Marc M   Gao Xin X   Jackson Jessica J   Rickels Ryan R   Swanson Selene K SK   Florens Laurence L   Washburn Michael P MP   Eissenberg Joel C JC   Shilatifard Ali A  

Science (New York, N.Y.) 20140801 6200


Histone H3 lysine(27)-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 H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various  ...[more]

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