Hundreds of gene regulatory motifs cooperate and conflict to make brain cells NatureComms
Experimental design. a Computational framework to select regions and perturbation sites. b Heatmap of motif instances in the assayed regions ; distribution of the number of motifs perturbed in each region ; distribution of the number of regions harboring each motif . c Library design; selected regions were included in their wild-type form, selected motifs were perturbed using three perturbation methods individually as well as in combination with other perturbations in selected cases .
, which target regulatory motifs in the enhancer sequence. Thus, interactions between enhancers and transcription factors are critical for enhancing or suppressing the genes that determine a cell's fate and behavior.and thus determine whether cells will grow into different organs. Despite their consequences, however, we understand relatively little about how enhancers function," explains Inoue.
and transcription factors. To extract even more information from the assays, we modified the assays to introduce perturbations in the regulatory motifs where transcription factors bind," continues Inoue. To validate their massively parallel reporter perturbation assay, the team applied it to the differentiation of human embryonic stem cells into neural cells. They found 598 regulatory motifs that either enhanced or dampened transcription.
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