Bhat K M, Farkas G, Karch F, Gyurkovics H, Gausz J, Schedl P
Department of Molecular Biology, Princeton University, NJ 08544, USA.
Development. 1996 Apr;122(4):1113-24. doi: 10.1242/dev.122.4.1113.
The GAGA protein of Drosophila was first identified as a stimulatory factor in in vitro transcription assays using the engrailed and Ultrabithorax promoters. Subsequent studies have suggested that the GAGA factor promotes transcription by blocking the repressive effects of histones; moreover, it has been shown to function in chromatin remodeling, acting together with other factors in the formation of nuclease hypersensitive sites in vitro. The GAGA factor is encoded by the Trithorax-like locus and in the studies reported here we have used the maternal effect allele Trl13C to examine the functions of the protein during embryogenesis. We find that GAGA is required for the proper expression of a variety of developmental loci that contain GAGA binding sites in their upstream regulatory regions. The observed disruptions in gene expression are consistent with those expected for a factor involved in chromatin remodeling. In addition to facilitating gene expression, the GAGA factor appears to have a more global role in chromosome structure and function. This is suggested by the spectrum of nuclear cleavage cycle defects observed in Trl13C embryos. These defects include asynchrony in the cleavage cycles, failure in chromosome condensation, abnormal chromosome segregation and chromosome fragmentation. These defects are likely to be related to the association of the GAGA protein with heterochromatic satellite sequences which is observed throughout the cell cycle.
果蝇的GAGA蛋白最初是在使用engrailed和Ultrabithorax启动子的体外转录试验中作为一种刺激因子被鉴定出来的。随后的研究表明,GAGA因子通过阻断组蛋白的抑制作用来促进转录;此外,已证明它在染色质重塑中起作用,在体外与其他因子共同作用形成核酸酶超敏位点。GAGA因子由类三胸座基因座编码,在本文报道的研究中,我们使用母体效应等位基因Trl13C来研究该蛋白在胚胎发育过程中的功能。我们发现,GAGA对于多种发育基因座的正确表达是必需的,这些基因座在其上游调控区域含有GAGA结合位点。观察到的基因表达破坏与参与染色质重塑的因子所预期的情况一致。除了促进基因表达外,GAGA因子似乎在染色体结构和功能中具有更广泛的作用。这是由在Trl13C胚胎中观察到的核分裂周期缺陷谱所表明的。这些缺陷包括分裂周期的不同步、染色体凝聚失败、异常的染色体分离和染色体片段化。这些缺陷可能与在整个细胞周期中观察到的GAGA蛋白与异染色质卫星序列的关联有关。