Identification of genes functionally involved in the detrimental effects of mutant histone H3.3-K27M in Drosophila melanogaster.

ABSTRACT:

Background

Recurrent specific mutations in evolutionarily conserved histone 3 (H3) variants drive pediatric high-grade gliomas (HGGs), but little is known about their downstream effects. The aim of this study was to identify genes involved in the detrimental effects of mutant H3.3-K27M, the main genetic driver in lethal midline HGG, in a transgenic Drosophila model.

Methods

Mutant and wild-type histone H3.3-expressing flies were generated using a φC31-based integration system. Genetic modifier screens were performed by crossing H3.3-K27M expressing driver strains and 194 fly lines expressing short hairpin RNA targeting genes selected based on their potential role in the detrimental effects of mutant H3. Expression of the human orthologues of genes with functional relevance i

SUBMITTER: Berlandi J 

PROVIDER: S-EPMC6502498 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature