The glial transcription factor Sox10 binds to DNA both as monomer and dimer with different functional consequences

Sox10 is an important transcriptional regulator in the neural crest and var ious neural-crest derived lineages, such as the Schwann cells of the periph eral nervous system. Recently, we identified the gene for myelin Protein ze ro (P-0) as a transcriptional target of Sox10 in Schwann cells, allowing fo r the first time a detailed analysis of Sox10 responsive elements and their functional interaction with Sox10. Here we show that Sox10 functions throu gh two different types of DNA response elements, one that allows binding of monomers, and a second that favors cooperative binding of two molecules. T his dimeric binding required the presence of two heptameric Sox binding sit es in a specific orientation and spacing, and was mediated by an N-terminal region of Sox10 with high conservation in the related Sox9, which also exh ibited dimeric binding, This argues that the conserved region has the capac ity to function as a DNA-dependent dimerization domain, The interaction bet ween Sox10 dimers and DNA differed dramatically from that of Sox10 monomers , as it drastically reduced the protein's off-rate and increased the protei n-induced angle of DNA bending, These results indicate that functionally re levant interactions between Sox10 and DNA occur through completely differen t modes of binding.