Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain

• Genome-scale enhancer identification is done in 136 regions of the adult human brain
• Enhancer enrichment varies across anatomical regions
• Coregulated enhancers represent cell type- and context-specific networks
• Alterations in newly identified enhancers are linked to Parkinson’s disease risk

SummaryUnderstanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson’s disease incidence.

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