Taveggia Carla, Pizzagalli Antonella, Fagiani Ernesta, Messing Albee, Feltri M Laura, Wrabetz Lawrence
San Raffaele Scientific Institute, DIBIT, Milan, Italy.
J Neurochem. 2004 Nov;91(4):813-24. doi: 10.1111/j.1471-4159.2004.02745.x.
Oligodendrocytes and Schwann cells use diverse regulatory elements to transcribe myelin basic protein (Mbp). For example, an enhancer 9.0 kb upstream of Mbp (MbpSCE1) activated either the proximal Mbp or hsp68 promoters only in Schwann cells in transgenic mice. Here, we analyze MbpSCE1 in vitro and in vivo and show that MbpSCE1 also activates another myelin gene, Mpz, specifically in Schwann cells in transgenic mice. Surprisingly, although MbpSCE1 behaves as an enhancer in Schwann cells, we show here for the first time that it also activates transcription robustly in cultured oligodendrocytes, but only from its original genomic position. Diverse nuclear proteins binding at distinct combinations of DNA elements in the two cell types may account for cell-specific MbpSCE1 function. A further surprise is that MbpSCE1 activation does not depend on consensus binding sites for the myelin-associated PPARbeta or Krox 20 transcription factors. Finally, chromatin context augments activation of MbpSCE1. Therefore, MbpSCE1 is active in both Schwann cells and oligodendrocytes, but by diverse mechanisms.
少突胶质细胞和施万细胞利用多种调控元件来转录髓鞘碱性蛋白（Mbp）。例如，Mbp上游9.0 kb处的一个增强子（MbpSCE1）在转基因小鼠中仅在施万细胞中激活近端Mbp或hsp68启动子。在此，我们在体外和体内分析了MbpSCE1，并表明MbpSCE1在转基因小鼠中也特异性地在施万细胞中激活另一个髓鞘基因Mpz。令人惊讶的是，尽管MbpSCE1在施万细胞中表现为增强子，但我们首次在此表明它在培养的少突胶质细胞中也能强有力地激活转录，但仅从其原始基因组位置起作用。两种细胞类型中不同的核蛋白以不同的DNA元件组合结合，这可能解释了MbpSCE1的细胞特异性功能。另一个令人惊讶的是，MbpSCE1的激活不依赖于髓鞘相关的PPARβ或Krox 20转录因子的共有结合位点。最后，染色质环境增强了MbpSCE1的激活。因此，MbpSCE1在施万细胞和少突胶质细胞中均有活性，但通过不同的机制。
