Interactions of Sox10 and Egr2 in myelin gene regulation
Interactions of Sox10 and Egr2 in myelin gene regulation
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DOI：
10.1017/s1740925x08000173
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发表时间：
2007-01-01
影响因子：
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通讯作者：
Svaren, John
中科院分区：
文献类型：
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作者：
Jones, Erin A.;Jang, Sung-Wook;Svaren, John
PNS的髓鞘形成是通过大量诱导髓鞘蛋白零（Mpz）基因产生最丰富的外周环磷酰胺蛋白来实现的。基因敲除分析表明，egr21krox20和SOXio转录因子是Mpz表达所必需的。我们最近的工作表明，与人类周围神经病变相关的显性EGIZ2注入导致特定位点的EGR21SOX协同作用中断，包括Mpz基因第一引入子中的11个保守增强子。对kgr2lSoxio相互作用的进一步研究表明，krz激活Mpz内含子需要两个soxio结合位点。此外，Lgri和Egr 3都与Soxio合作激活了该元素，这表明该能力在k种分子中是保守的。最后，利用编码Mpz、叶磷脂相关糖蛋白和叶磷脂基本蛋白基因的基因中egr2lsoxio结合位点的保守共正子结构，筛选其他叶磷脂基因中类似的内含物，揭示了环轴蛋白基因中潜在的调控元件。总的来说，这些结果阐明了Mpz表达的发育调控的工作模型，几个jj -延伸到其他外周ruyelin基因的调控。
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.