RRC ID 57204
Author Drelon C, Belalcazar HM, Secombe J.
Title The Histone Demethylase KDM5 Is Essential for Larval Growth in Drosophila.
Journal Genetics
Abstract Regulated gene expression is necessary for developmental and homeostatic processes. The KDM5 family of transcriptional regulators are histone H3 lysine 4 demethylases that can function through both demethylase-dependent and -independent mechanisms. While loss and overexpression of KDM5 proteins are linked to intellectual disability and cancer, respectively, their normal developmental functions remain less characterized. Drosophila melanogaster provides an ideal system to investigate KDM5 function, as it encodes a single ortholog in contrast to the four paralogs found in mammalian cells. To examine the consequences of complete loss of KDM5, we generated a null allele of Drosophila kdm5, also known as little imaginal discs (lid), and show that it is essential for viability. Animals lacking KDM5 show a dramatically delayed larval development that coincides with decreased proliferation and increased cell death in wing imaginal discs. Interestingly, this developmental delay is independent of the well-characterized Jumonji C (JmjC) domain-encoded histone demethylase activity of KDM5, suggesting key functions for less characterized domains. Consistent with the phenotypes observed, transcriptome analyses of kdm5 null mutant wing imaginal discs revealed the dysregulation of genes involved in several cellular processes, including cell cycle progression and DNA repair. Together, our analyses reveal KDM5 as a key regulator of larval growth and offer an invaluable tool for defining the biological activities of KDM5 family proteins.
Volume 209(3)
Pages 773-787
Published 2018-7
DOI 10.1534/genetics.118.301004
PII genetics.118.301004
PMID 29764901
PMC PMC6028249
MeSH Animals Cell Cycle Cell Death Cell Proliferation DNA Repair Drosophila Proteins / chemistry Drosophila Proteins / genetics* Drosophila Proteins / metabolism Drosophila melanogaster / genetics Drosophila melanogaster / growth & development* Drosophila melanogaster / metabolism* Gene Expression Regulation, Developmental Gene Regulatory Networks* Histone Demethylases / chemistry Histone Demethylases / genetics* Histone Demethylases / metabolism Larva / growth & development Larva / metabolism Loss of Function Mutation* Phenotype Protein Domains Sequence Analysis, RNA Wings, Animal / growth & development*
IF 3.564
Times Cited 5