A long-standing goal of evolutionary biology is to decode how changes in gene regulatory networks contribute to human-specific traits. Human accelerated regions (HARs) are prime candidates for driving gene regulatory modifications in human development. The locus is densely populated with HARs, providing a set of potential regulatory elements that could have changed its expression in the human lineage. Here, we examined the role of -HARs using transgenic zebrafish reporter assays and identified 15 transcriptional enhancers that are active in the developing nervous system, 9 of which displayed differential activity between the human and chimpanzee sequences. The engineered loss of two selected -HARs in knockout mouse models modified expression at specific developmental stages and tissues in the brain, influencing the expression and splicing of a high number of target genes. Our results provided insight into the spatial and temporal changes in gene expression driven by -HARs.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11204294 | PMC |
| http://dx.doi.org/10.1126/sciadv.adl1049 | DOI Listing |
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