1. Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus.
- Author
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Berasain, Lara, Beati, Paula, Trigila, Anabella P., Rubinstein, Marcelo, and Franchini, Lucía F.
- Subjects
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GENE regulatory networks , *HUMAN evolution , *NEURAL development , *GENE expression , *REGULATOR genes , *RNA splicing - Abstract
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 RBFOX1 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 RBFOX1-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 RBFOX1-HARs in knockout mouse models modified Rbfox1 expression at specific developmental stages and tissues in the brain, influencing the expression and splicing of a high number of Rbfox1 target genes. Our results provided insight into the spatial and temporal changes in gene expression driven by RBFOX1-HARs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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