Interactions of Sox10 and Egr2 in myelin gene regulation

Myelination in file PNS is accouipanicd by a large induction of the inyelin protein zero (Mpz) gene to produce the inost abundant cornponeut in peripheral rnyclin. Analyses of knockout unce have shown that the EGR21Krox2o and SOXio transcription factors are required for Mpz expression. Our recent work has shown that the doininant EGIZ2 inufations associated with hunian peripheral neuropathies cause disruption of EGR21SOX o synergy at specific sites, including 11 conserved enhancer clenient in the first introit of the Mpz gene. Further investigation of kgr2lSoxio interactions reveals that activation of the Mpz intron clernent by k rz requires both Soxio-binding sites. In addition, both Lgri and Egr 3 cooperate with Soxio to activate this elenient, which indicates that this capacity is conserved ainong k rjarnily inenibers. Finally, a conserved coinpositc structure of Egr2lSoxio-binding sites in the genes encoding Mpz, aiyelin-associated glycoprotcin and inyelin basic protein genes was used to screen for sinlilar inodules in other ntyclin genes, revealing a potential regulatory eletnent in the periaxin gene. Overall, these results elucidate a working inodelfor developniental regulation of Mpz expression, several jacets oj- which extend to regulation of other peripheral ruyelin genes.