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Derepression of inflammation-related genes link to microglia activation and neural maturation defect in a mouse model of Kleefstra Syndrome

ABSTRACT: Kleefstra syndrome (KS, also known as 9q.34.3 deletion syndrome) is a rare genetic disorder characterized by a developmental delay, abnormal behaviors and autism-like features. This syndrome is caused by haplo-insufficiency of the euchromatin histone methyltransferase 1 gene (EHMT1/GLP/KDM1D). This gene product, GLP is a methyltransferase responsible for mono- and di-methylation of lysine 9 on histone H3 N-terminal tail, which modulates epigenetic information. Ehmt1 heterozygous mutant (Ehmt1∆/+) mice show KS-like abnormal behavioral phenotypes and utilized as KS model mice. Here, we isolated nuclei from adult Ehmt1∆/+ mice cortex and analysed gene expression precisely by single nucleus RNA-seq analysis. It showed that many genes were up or down regulated in different cell types of Ehmt1∆/+ mice brain. Among them, inflammation associating genes are up-regulated in Ehmt1∆/+ mice neuronal cells. And this up-regulation was reversed by postnatal supply of GLP in post-mitotic neuron of Ehmt1∆/+ mice brain.

ORGANISM(S): Mus musculus

PROVIDER: GSE162934 | GEO | 2021/06/11

REPOSITORIES: GEO

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Post-natal supply of GLP/Ehmt1 reverses Histone H3K9 dimethylation in cortical neuron isolated from adult Ehmt1∆/+ mice brain

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Rattus norvegicus

Project description:Histone methylation by the Kleefstra Syndrome protein EHMT1 mediates homeostatic synaptic scaling.

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