SOX2 transcriptional regulation by enhancer elements: a comprehensive review with a unified enhancer nomenclature

Transcription factor SOX2 is essential for a number of biological processes, including mammalian nervous system development and adult brain stem cell maintenance. Expression of this gene requires precise control by a complex network of regulatory elements, which still remains poorly understood. Years of research by different groups have generated a large amount of data on multiple SOX2 enhancers, with varying levels of evidence for their activity across species and tissues. However, the volume of information in the field and inconsistent nomenclature, with the same enhancer referred to by different study-specific names, make understanding progress in SOX2 enhancer regulation challenging. In this review, we brought together current knowledge on predicted and experimentally validated SOX2 enhancers, highlighting links between conserved elements studied in different species. We also propose a unified enhancer naming system based on the distance from the SOX2 transcription start site in the genome of interest, aiming to improve consistency and make communication in the field more straightforward.