Characterization of enhancer activity in early human neurodevelopment using Massively parallel reporter assay (MPRA) and forebrain organoids.

ABSTRACT: Regulation of gene expression through enhancers is one of the major processes shaping the structure and function of the human brain during development. High-throughput assays have predicted thousands of enhancers involved in neurodevelopment, and confirming their activity through orthogonal functional assays is crucial. Here, we utilized Massively Parallel Reporter Assays (MPRAs) in stem cells and forebrain organoids to evaluate the activity of ~7,000 gene-linked enhancers previously identified in human fetal tissues and brain organoids. We used a Gaussian mixture model to evaluate the contribution of background noise in the measured activity signal to confirm the activity of ~35% of the tested enhancers, with most showing temporal-specific activity, suggesting their evolving role in neuro

SUBMITTER: Capauto D 

PROVIDER: S-EPMC10461976 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature