Fig. 5: Loss of MEF2C remodels the active enhancer landscape.

a, Scatter plot of H3K27ac ChIP–seq signal around distal (>1,000 base pairs (bp) from TSS) ATAC–seq peaks in MEF2C control and KO iMGs (ATAC–seq: n = 3 control and 2 KO; H3K27ac ChIP–seq: n = 4 control and 4 KO iMG biological samples derived from independent iPS cell lines from separate differentiation batches). Differentially acetylated regions enriched in control iMGs are defined by DESeq2 as an FDR of <0.05 and log₂ (FC) of <–1 and enriched in KO iMGs as an FDR of <0.05 and log₂ (FC) of >1. b, De novo motif analysis of differentially acetylated regions enriched in control (top) and KO iMGs (bottom). GC-matched sequences were used as background (BG). c, Bar chart showing gene expression of transcription factors whose DNA-binding motifs were identified in b. FDR determined by DESeq2. d, Bubble plot derived from de novo motif analysis of differentially acetylated regions, delineating transcription factor DNA-binding motif enrichment for all MEF2C genotypes (ATAC–seq: n = 3 control, 2 MHS and 2 KO; H3K27ac ChIP–seq: n = 4 control, 4 MHS and 4 KO iMG biological samples derived from independent iPS cell lines from separate differentiation batches). e, Differentially acetylated peaks from Ramaswami et al.⁵³ between control and idiopathic autism frontal and cortical brain samples, which were annotated for overlap with cell-type-specific promoter (left) and enhancer (right) peaks from Nott et al.²³. f, Overlaps between genes nearest to differentially acetylated peaks in idiopathic autism compared to control brain tissue (Ramaswami et al.⁵³) and genes nearest to H3K27ac-marked distal ATAC peaks in control (left), MHS (middle) and KO iMGs (right). P values were determined using hypergeometric tests.