Fig. 3: Cell-type-specific nature of epigenetic dysregulation in AD.
From: Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders
a We built AD-associated gene regulatory networks by linking genes to hypoacetylated (hypo) and hyperacetylated (hyper) peaks in AD via Hi–C interactions in NeuN+ and NeuN− cells. b AD-associated hyperacetylated peaks were largely active in NeuN− cells, while AD-associated hypoacetylated peaks are largely active in NeuN+ cells in neurotypical controls. c The number of genes mapped to AD-associated hyperacetylated (top) and hypoacetylated (bottom) peaks via Hi–C interactions in NeuN+ and NeuN− cells. CACNG3 is linked to an AD-associated hypoacetylated peak (marked in yellow) in NeuN+ cells (d), while EHD1 is linked to an AD-associated hyperacetylated peak (marked in yellow) in NeuN− cells (e). CACNG3/EHD1 promoter is highlighted in gray and its interacting regions are highlighted in green and purple for NeuN+ and NeuN− cells, respectively. Boxplots in the right show expression levels of CACNG3/EHD1 in NeuN+ (n = 4) and NeuN− (n = 4) cells. FPKM Fragments Per Kilobase of transcript per Million mapped reads. Center, median; box = Q1–Q3; minima, Q1 − 1.5 × IQR; maxima, Q3 + 1.5 × IQR. *FDR < 0.05 (FDR = 2.81e−9 for CACNG3 and FDR = 0.004 for EHD1), calculated by DESeq2 (two-sided Wald test). Source data are provided as a Source Data file. f NeuN+ hypoacetylated genes are highly expressed in neurons, while NeuN− hyperacetylated genes are highly expressed in glia. g NeuN− hyperacetylated genes are enriched in astrocyte-specific co-expression modules (T-M14 and T-M8) that are upregulated in AD. NeuN+ hypoacetylated genes are enriched in neuronal co-expression modules (T-M1, T-M16) that are downregulated in AD. Fisher’s exact test was used for statistical analysis. The red line denotes FDR = 0.01. Astro astrocytes, Micro microglia, Endo endothelial, Oligo oligodendrocytes.
