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The epigenetic reader PHF21B modulates social memory and synaptic plasticity-related genes in mice

ABSTRACT: Plant homeodomain (PHD) finger proteins are epigenetic readers whose dysfunctions are implicated in neurological conditions, but the molecular mechanisms linking PHD protein deficits to disease remain unclear. Here we generated a PHD finger protein 21B (Phf21b)-depleted mutant CRISPR mouse model (Phf21bΔ4/Δ4) to examine its roles in the brain. KO animals exhibited impaired social memory. Reduced expression of synaptic proteins and impaired long-term potentiation were observed in the KO hippocampi. Transcriptome profiling revealed differential expression of genes involved in synaptic plasticity processes. Furthermore, we characterized a novel interaction of PHF21B to H3K36me3 (histone H3 tri-methylated lysine 36), a histone modification associated with transcriptional activation, and the transcriptional factor CREB. These results establish PHF21B as an important upstream regulator of synaptic plasticity-related genes, and a candidate therapeutic target for murine neurobehavioral dysfunction, with potential applications in human neurological and psychiatric disorders.

ORGANISM(S): Mus musculus

PROVIDER: GSE201477 | GEO | 2022/09/15

REPOSITORIES: GEO

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