Characterizing the dynamic epigenome-transcriptome landscape that controls formation of the vertebrate body axis

Characterizing the dynamic epigenome-transcriptome landscape that controls formation of the vertebrate body axis

Speaker: Professor Andrea Münsterberg, School of Biological Sciences, University of East Anglia

Host: Dr Elisabeth Ehler

Abstract: The vertebrate body axis is generated by transient embryonic structures called somites, which form as paired segments on either side of the developing spinal cord. Somites are of fundamental importance as they generate the lineages of the musculoskeletal system, including the cartilage of the vertebral column and ribs, skeletal muscles and axial tendons. The progressive commitment of cells to adopt these cell fates is coordinated by networks of signalling molecules that regulate differential gene expression during developmental transitions along with the head to the tail axis. The sequence of marker gene expression during somite differentiation is well defined, however, the epigenetic and genomic mechanisms that control these transcriptional programmes remain largely unknown. We used ATAC-seq to reveal chromatin accessibility in differentiating somites along the axis. This was correlated with differential RNAseq to examine the heterogeneity of genes expressed. We focused on early musculoskeletal development and identified novel cis-regulatory elements in the vicinity of mesodermal genes. The CREs were validated in vivo by electroporation into chick embryos, followed by live microscopy to visualise their spatio-temporal activity. Furthermore, in silico footprint analysis and mutation of candidate TF binding sites revealed elements crucial for CRE activity.