Fig. 3: promoter-isoform alternations between brain regions.

a Schematic representation of promoter-isoform quantification using RNA-seq data from neurons. Transcripts that are regulated by the same promoter are grouped (promoter-isoform), and are quantified using the set of unique junction reads spanning the first intron of each transcript. The non-uniquely identifiable promoter-isoforms (red) were removed from this analysis (Methods). b Spearman correlation coefficient (SCC) between the log2 fold change of gene/promoter-isoform and promoter OCR across brain regions. N indicates the number of non-concordant promoter-isoforms. Gene promoter OCRs were determined using the 5′ most promoter region. c Upper panel, the promoter-isoform expression and promoter OCR chromatin accessibility level across brain regions. For RNA-seq, N_ForeBr = 84, N_BasGan = 15, N_MidDien = 27. For ATAC-seq N_ForeBr = 67, N_BasGan = 9, N_MidDien = 17. Box plot indicates median, interquartile range (IQR) and 1.5× IQR. Bottom panel, chromatin accessibility profiles (neuronal), and the position of the two promoter-isoforms (highlighted in black boxes). d Enrichment of common variants for different trait classes at the DEGs, and promoter-isoform-specific DEGs for each comparison (fine brain region) or each brain region (broad brain region) determined by MAGMA¹⁰⁶. The y-axis represents the enrichment level (MAGMA beta ± standard error, se), and the size represents the FDR value. “·”: Nominally significant (P < 0.05); “+”: significant after FDR correction (FDR < 0.05). e Rare variants, loss of function intolerant genes (pLI0.9), and biological pathways enrichment of the genes that exhibit promoter-isoform-specific DEGs determined by one-tailed Fisher’s exact test. FDR corrections were performed using the Benjamini & Hochberg method.