Stimulating Wnt signaling reveals context-dependent genetic effects on gene regulation in primary human neural progenitors.

ABSTRACT: Gene regulatory effects have been difficult to detect at many non-coding loci associated with brain-related traits, likely because some genetic variants have distinct functions in specific contexts. To explore context-dependent gene regulation, we measured chromatin accessibility and gene expression after activation of the canonical Wnt pathway in primary human neural progenitors (n = 82 donors). We found that TCF/LEF motifs and brain-structure-associated and neuropsychiatric-disorder-associated variants were enriched within Wnt-responsive regulatory elements. Genetically influenced regulatory elements were enriched in genomic regions under positive selection along the human lineage. Wnt pathway stimulation increased detection of genetically influenced regulatory elements/genes by 66%/53%

SUBMITTER: Matoba N 

PROVIDER: S-EPMC11633645 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature