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Sagot :
Large clusters of hyper-acetylated CRDs with prominent representation of regulatory sequences governing foetal development and glutamatergic neuron signalling were enriched for SCZ heritability. Therefore, risk-associated regulatory sequences assembled into kilobase- to mega base-scaling chromosomal domains exhibit coordinated dysregulation in SCZ and BD brains.
The structure of the chromosomes in the human brain, from the 147-base pair (bp) nucleosome to megabase-ranging regions including several transcriptional units, including heredity loci for mental characteristics, is still mostly unknown. In this study, we generated H3-lysine 27 acetylation and H3-lysine 4 trimethylation profiles from 388 controls and 351 people with schizophrenia (SCZ) or bipolar disorder (BD) (n = 739). From these profiles, we constructed promoter- and enhancer-enriched nucleosomal histone modification landscapes for adult prefrontal cortex. Thousands of cis-regulatory domains (CRDs) were mapped, demonstrating fine-grained chromosomal structure of 104–106 bp that was tightly incorporated into Hi-C topologically associating domain stratification by open/repressive chromosomal settings and nuclear topography.
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