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Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus.

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.

SUBMITTER: Berasain L 

PROVIDER: S-EPMC11204294 | biostudies-literature | 2024 Jun

REPOSITORIES: biostudies-literature

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Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the <i>RBFOX1</i> locus.

Berasain Lara L   Beati Paula P   Trigila Anabella P AP   Rubinstein Marcelo M   Franchini Lucía F LF  

Science advances 20240626 26

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 <i>RBFOX1</i> 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 <i>RBFOX1</i>-HARs using transgenic zebrafish repor  ...[more]

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