PUBLICATION
Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus
- Authors
- Berasain, L., Beati, P., Trigila, A.P., Rubinstein, M., Franchini, L.F.
- ID
- ZDB-PUB-240627-10
- Date
- 2024
- Source
- Science advances 10: eadl1049 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Humans
- Mice
- Zebrafish*/genetics
- Mice, Knockout
- Animals
- Pan troglodytes/genetics
- Enhancer Elements, Genetic*
- Gene Expression Regulation, Developmental
- Animals, Genetically Modified
- Evolution, Molecular*
- Gene Regulatory Networks
- Genetic Loci
- RNA Splicing Factors*/genetics
- RNA Splicing Factors*/metabolism
- PubMed
- 38924416 Full text @ Sci Adv
Citation
Berasain, L., Beati, P., Trigila, A.P., Rubinstein, M., Franchini, L.F. (2024) Accelerated evolution in the human lineage led to gain and loss of transcriptional enhancers in the RBFOX1 locus. Science advances. 10:eadl1049.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping