The Histone Demethylase KDM5 Is Essential for Larval Growth in Drosophila

Genetics
Coralie DrelonJulie Secombe

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 imagin...Continue Reading

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Citations

Oct 4, 2020·Experimental Cell Research·R KirtanaSamir Kumar Patra
Jun 6, 2021·American Journal of Medical Genetics. Part a·Hayden A M HatchLisa H Shulman

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Datasets Mentioned

BETA
GSE109201
GSE70591
GSE27081
GSZ53881
GSE68775

Methods Mentioned

BETA
transgenic
PCR
light microscopy
Illumina
RNA-seq
immunoprecipitation
irradiating
ChIP-seq
ChIP
1-hybrid

Software Mentioned

R
COR Odyssey
DESeq2
ImageJ
GraphPad Prism
STAR aligner
FlyMine
GraphPad
LI
GOrilla

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