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Sox3/SOX3  is one of the earliest neural markers in vertebrates. Together with the  Sox1/SOX1  and  Sox2/SOX2  genes it is implicated in the regulation of stem cell identity. In the present study, we performed the first analysis of epigenetic mechanisms (DNA methylation and histone marks) involved in the regulation of the human  SOX3  gene expression during RA-induced neural differentiation of NT2/D1 cells. We show that the promoter of the human  SOX3  gene is extremely hypomethylated both in undifferentiated NT2/D1 cells and during the early phases of RA-induced neural differentiation. By employing chromatin immunoprecipitation, we analyze several histone modifications across different regions of the  SOX3  gene and their dynamics following initiation of differentiation. In the same timeframe we investigate profiles of selected histone marks on the promoters of human S OX1  and  SOX2  genes. We demonstrate differences in histone signatures of  SOX1 ,  SOX2  and  SOX3  genes. Considering the importance of  SOXB1  genes in the process of neural differentiation, the present study contributes to a better understanding of epigenetic mechanisms implicated in the regulation of pluripotency maintenance and commitment towards the neural lineage.

Epigenetic regulation of human SOX3 gene expression during early phases of neural differentiation of NT2/D1 cells