ArticleFrontiers in genetics2026
Epigenetic regulators are preferentially coordinated with protocadherin gene expression across the human brain: a genome-wide co-expression analysis.
Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
How does the brain build and maintain the precise wiring patterns that distinguish one neuron from another? Clustered protocadherins (PCDHs)-a family of cell-surface molecules that give each neuron a unique identity tag-are central to this process. Their expression is famously controlled by an elaborate locus-specific epigenetic system involving DNA methylation, CTCF binding, and chromatin looping. Whether the activity of the broader epigenetic regulatory machinery is coordinated with protocadherin expression across the human brain has not been systematically tested. Here we show that epigenetic regulators are preferentially co-expressed with protocadherins across multiple human brain regions, suggesting a broader transcriptional coordination than the locus-specific mechanisms previously characterized. Using GTEx v8 RNA-seq data from 2,642 brain samples across 13 regions, we conducted a genome-wide co-expression screen and observed a 6.5-fold enrichment of epigenetic regulators in the top 5% of PCDH-coordinated genes in prefrontal cortex (Fisher's exact p = 2.8 × 10
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