Regulation of Sox2 via Many Enhancers of Distinct Specificities

Abstract SOX2 has many different roles depending on the developmental stage, tissue, and type of cancer. Enhancers that activate the Sox2 gene under different developmental contexts vary widely and are distributed over hundreds of kilobases of the genomic span centered on the Sox2 gene. Our survey on embryonic neural and sensory primordial development identified 26 active enhancers that are distinct in their timing and tissue coverage. Additional enhancers likely exist, possibly as a subset of conserved sequence blocks identified by comparing human and chicken Sox2 locus sequences. The N2 and N1 enhancers were activated earliest during embryogenesis to regulate Sox2 in the developing anterior and posterior neural plates. Detailed analysis of the regulation and action of these enhancers reveals the mechanisms underlying the genesis of the anterior and posterior neural plates. An example is that the posterior neural plate develops from axial stem cells with neural and mesodermal bipotentiality.