Leveraging chicken embryos for studying human enhancers

The dynamic activity of complex gene regulatory networks stands at the core of all cellular functions that define cell identity and behaviour. Gene regulatory networks comprise transcriptional enhancers, acted upon by cell-specific transcription factors to control gene expression in a spatial and temporal specific manner. Enhancers are found in the non-coding genome; pathogenic variants can disrupt enhancer activity and lead to disease. Correlating non-coding variants with aberrant enhancer activity remains a significant challenge. Due to their clinical significance, there is a longstanding interest in understanding enhancer function during early embryogenesis. With the onset of the omics era, it is now feasible to identify putative tissue-specific enhancers from epigenome data. However, such predictions in vivo require validation. The early stages of chick embryogenesis closely parallel those of human, offering an accessible in vivo model in which to assess the activity of putative human enhancer sequences. This review explores the unique advantages and recent advancements in employing chicken embryos to elucidate the activity of human transcriptional enhancers and the potential implications of these findings in human disease.