Stankoff B, Demerens C, Goujet-Zalc C, Monge M, Peyron F, Mikoshiba K, Zalc B, Lubetzki C
Laboratoire de Neurobiologie Cellulaire, Moléculaire et Clinique, INSERM U-134, Hôpital de la Salpêtrière, Université Pierre et Marie Curie, Paris, France.
Mult Scler. 1996 Oct;2(3):125-32. doi: 10.1177/135245859600200302.
Myelination in the central nervous system requires synthesis by oligodendrocytes of enormous amounts of lipids and proteins for incorporation in the developing myelin membranes. To approach the regulatory events coordinating the transcriptional activation of the genes that encode myelin proteins, we examined control of the myelin basic protein (MBP) locus. MBP plays a major role in myelin compaction. During development, MBP is already expressed in mature non-myelinating oligodendrocytes. Here we show that, in transgenic animals in which the E. coli lacZ reporter gene is under the control of increasingly large portions (256, 1900 and 3200 bp) of the MBP promoter, 5' of the initiation of transcription site, reporter gene expression was initiated after myelin formation had started. This delayed expression of the transgene compared to MBP, strongly suggests that premyelinating expression is dependent on regulatory elements located outside of the 3200 bp sequence studied, while expression occurring at the time of myelin formation is dependent on the proximal promoter sequence.
中枢神经系统的髓鞘形成需要少突胶质细胞合成大量脂质和蛋白质，以纳入正在发育的髓鞘膜中。为了探究协调髓鞘蛋白编码基因转录激活的调控事件，我们研究了髓鞘碱性蛋白（MBP）基因座的调控。MBP在髓鞘紧密化中起主要作用。在发育过程中，MBP已在成熟的未髓鞘化少突胶质细胞中表达。在此我们表明，在大肠杆菌lacZ报告基因受MBP启动子转录起始位点上游越来越大片段（256、1900和3200 bp）控制的转基因动物中，报告基因表达在髓鞘形成开始后才启动。与MBP相比，转基因的这种延迟表达强烈表明，髓鞘形成前的表达依赖于所研究的3200 bp序列之外的调控元件，而在髓鞘形成时发生的表达则依赖于近端启动子序列。
