Brain cell type–specific enhancer–promoter interactome maps and disease - risk association
Картирование взаимодействий энхансер–промотор (интерактом) по типам клеток мозга и связь с риском заболеваний
2019-11-14
SCID: 54.1/2ftrs93k
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Alzheimer's disease risk variantsBIN1 microglia enhancer deletionbrain cell type–specific enhancer–promoter interactomecell-type-specific enhancersmicroglia enhancersmicroglia gene networkneuronal enhancers and promotersnoncoding regulatory regions
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Abstract (AI)
Linking enhancers to disease Enhancers are genomic regions that regulate gene expression, sometimes in a cell-dependent manner. However, most of our knowledge of human brain cell–type enhancers derives from studies of bulk human brain tissue. Nott et al. examined chromatin and promoter activity in cell nuclei isolated from human brains. Genetic variants associated with brain traits and disease showed cell-specific patterns of enhancer enrichment. These data indicate that Alzheimer's disease is regulated by genetic variants within microglial cells, whereas psychiatric diseases tend to affect neurons. Science , this issue p. 1134
Key Findings
1
Defined noncoding regulatory regions (enhancers and promoters) for major human brain cell types to interpret genetic variation.
2
Deletion of a microglia-specific enhancer containing AD-risk variants abolished BIN1 expression in microglia but not in neurons or astrocytes.
3
Findings expand the list of genes likely influenced by noncoding variants in AD and indicate the probable cell types mediating their effects.
4
Interactome maps linking cell-type-specific enhancers to promoters reveal an extended microglia gene network implicated in AD.
5
Psychiatric disorder-associated variants are primarily enriched in enhancers and promoters of neurons.
6
Sporadic Alzheimer's disease (AD) associated variants are largely confined to microglia enhancers.
Research Object
Cell type–specific enhancer–promoter interactome maps for major human brain cell types (neurons, microglia, astrocytes)
Research Subject
Associations between noncoding genetic variants (disease-risk variants) and target gene regulation via cell type–specific enhancers and promoters, including mapping enhancer-promoter interactions that link variants to altered gene expression in specific brain cell types (notably microglia in Alzheimer's disease)
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2019-11-14
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