Figure 3. Higher order chromatin changes at the MEF2C locus in some cases with schizophrenia.

(A) H3K4me3 ChIP-seq genome browser tracks from PFC neuron chromatin of four representative control (blue) and five representative schizophrenia (red) subjects (left) 700kb MEF2C and (center) 120kb CAMK2A locus. Notice increased H3K4me3 around MEF2C transcription start site (dotted rectangle) in 2/5 disease cases. (right) Bargraph, H3K4me3 read density (total N=34 subjects, mean±S.E.M.) at 450bp regulatory MEF2C sequence (HG19 chromosome 5:88,179,454–88,179,902). Data show N=17 controls, N=17 disease cases, P<0.05, two-tailed t-test. Note MEF2C motif at chr5: 88,178,935–88,178,961, in close proximity to MEF2C transcription start site. (B) Genomic landscape in human PFC at MEF2C locus. ChIP-seq track showing multiple broad (>50kb) stretches of histone H3K27 acetylated sequence, including two superenhancer (SE) ²⁷ at MEF2C 5’ and 3’ end. Two top scoring SNPs associated with genetic risk for schizophrenia ⁶³ and Alzheimer’s disease⁶⁴, as indicated. (C) PFC higher order chromatin mapping with chromosome conformation capture (3C) from N=7 diseased (SCZ, red) and N=4 controls (CON, blue) subjects. 3C-PCR anchor ‘A’ primer and loop-bound DNA with primers no.1–12 as indicated. Notice there are no consistent alterations in the disease cohort.