Miller A A, Bernardoni R, Giangrande A
Institut de Génétique et Biologie Moléculaire et Cellulaire, IGBMC/CNRS/INSERM/ULP, BP 163 67404 Illkirch, Communauté Urbaine de Strasbourg, France.
EMBO J. 1998 Nov 2;17(21):6316-26. doi: 10.1093/emboj/17.21.6316.
Fly gliogenesis depends on the glial-cell-deficient/glial-cell-missing (glide/gcm) transcription factor. glide/gcm expression is necessary and sufficient to induce the glial fate within and outside the nervous system, indicating that the activity of this gene must be tightly regulated. The current model is that glide/gcm activates the glial fate by inducing the expression of glial-specific genes that are required to maintain such a fate. Previous observations on the null glide/gcmN7-4 allele evoked the possibility that another role of glide/gcm might be to maintain and/or amplify its own expression. Here we show that glide/gcm does positively autoregulate in vitro and in vivo, and that the glide/gcmN7-4 protein is not able to do so. We thereby provide the first direct evidence of both a target and a regulator of glide/gcm. Our data also demonstrate that glide/gcm transcription is regulated at two distinct steps: initiation, which is glide/gcm-independent, and maintenance, which requires glide/gcm. Interestingly, we have found that autoregulation requires the activity of additional cell-specific cofactors. The present results suggest transcriptional autoregulation is a mechanism for glial fate induction.
果蝇神经胶质细胞生成依赖于神经胶质细胞缺陷/神经胶质细胞缺失(glide/gcm)转录因子。glide/gcm的表达对于在神经系统内外诱导神经胶质细胞命运而言是必要且充分的,这表明该基因的活性必须受到严格调控。当前的模型认为,glide/gcm通过诱导维持这种命运所需的神经胶质细胞特异性基因的表达来激活神经胶质细胞命运。先前对无效的glide/gcmN7 - 4等位基因的观察引发了一种可能性,即glide/gcm的另一个作用可能是维持和/或放大其自身的表达。在这里,我们表明glide/gcm在体外和体内确实存在正向自我调节,而glide/gcmN7 - 4蛋白则无法做到这一点。我们从而提供了glide/gcm的一个靶标和一个调节因子的首个直接证据。我们的数据还表明,glide/gcm转录在两个不同步骤受到调控:起始阶段,该阶段不依赖于glide/gcm;维持阶段,该阶段需要glide/gcm。有趣的是,我们发现自我调节需要额外的细胞特异性辅因子的活性。目前的结果表明转录自我调节是一种诱导神经胶质细胞命运的机制。