Fig. 2: Genome-wide changes of chromatin state in the post-mortem striatum.

a Factors contributing to ATAC-seq signal variability. Violin plots showing the percentage of ATAC-seq signal variance explained by cell type (neuronal or non-neuronal), diagnosis (heroin vs. control; shown separately in neuron and non-neuronal cells), gender, individual variability, post-mortem interval, and residual factors. Top genes are indicated next to the plots. Within neurons, heroin-use group (heroin vs. control) was the primary source of variability. In this cell population, a peak close to the FYN gene ranked first as the signal whose variance was most influenced by drug group. PMI: post-mortem interval. Boxplots indicate median, 25th and 75 quantiles. The whiskers are definted as 1.5× inter-quartile range (IQR). b, c Heat maps of differentially accessible regions in neuronal (b) and non-neuronal (c) cell populations revealed marked quantitative group differences. d Enriched gene ontology categories for neuronal ATAC-seq peaks that are less accessible in heroin users (minimum hypergeometric test). e Enriched gene ontology categories for neuronal ATAC-seq peaks that are more accessible in heroin users include terms related to synaptic function and membrane receptor activity (minimum hypergeometric test). f, g Volcano plots showing differentially accessible regions in heroin users compared to controls in neuronal (f) and non-neuronal (g) cell populations. Significant non-neuronal peaks are marked in blue on the neuronal plot (f) and significant neuronal peaks are marked in red on the non-neuronal plot (g). More regions were significantly affected by heroin in neurons, whereas regions affected in glia were mostly shared between the two cell populations. PMI post-mortem interval.