Neuronal and glial 3D chromatin architecture informs the cellular etiology of brain disorders.

ABSTRACT: Cellular heterogeneity in the human brain obscures the identification of robust cellular regulatory networks, which is necessary to understand the function of non-coding elements and the impact of non-coding genetic variation. Here we integrate genome-wide chromosome conformation data from purified neurons and glia with transcriptomic and enhancer profiles, to characterize the gene regulatory landscape of two major cell classes in the human brain. We then leverage cell-type-specific regulatory landscapes to gain insight into the cellular etiology of several brain disorders. We find that Alzheimer's disease (AD)-associated epigenetic dysregulation is linked to neurons and oligodendrocytes, whereas genetic risk factors for AD highlighted microglia, suggesting that different cell types may co

SUBMITTER: Hu B 

PROVIDER: S-EPMC8233376 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature