Frasch M
Max-Planck-Institut für Entwicklungsbiologie, Tübingen, FRG.
EMBO J. 1991 May;10(5):1225-36. doi: 10.1002/j.1460-2075.1991.tb08064.x.
Using monoclonal antibodies I have identified a nuclear protein of Drosophila, BJ1 (Mr approximately 68 kd), and isolated its gene. Biochemical analysis demonstrates that the BJ1 protein is associated with nucleosomes and is released from chromatin by agents which intercalate into DNA, as previously shown for the high mobility group proteins (HMGs). On polytene chromosomes the protein is localized in all bands, with no preference for particular loci. Both the BJ1 protein and in particular the BJ1 mRNA are strongly expressed maternally. In early embryos all nuclei contain equal amounts of BJ1. During neuroblast formation, BJ1 mRNA becomes restricted to cells of the central nervous system, and higher protein levels are found in the nuclei of this tissue. In late embryonic stages, the mRNA almost completely disappears, but significant amounts of BJ1 protein persist until morphogenesis. The BJ1 gene encodes a 547 amino acid polypeptide featuring two different types of internal repeats. The sequence from amino acids 46 to 417 containing seven repeats of the first type has been highly conserved in evolution. 45% of the amino acids in this region are conserved in seven similar tandem repeats of the human gene Regulator of Chromatin Condensation, RCC1. The phenotype of a cell line carrying a mutation of RCC1 suggested a main function for this gene in cell cycle control. A yeast gene, SRM1/PRP20, also contains these repeats and shows 30% amino acid identity to BJ1 in this region. Mutations in this gene perturb mRNA metabolism, disrupt nuclear structure and alter the signal transduction pathway for the mating pheromone. Complementation experiments argue for a common function of these genes in the different species. I propose that their gene products bind to the chromatin to establish or maintain a proper higher order structure as a prerequisite for a regulated gene expression. Disruption of this structure could cause both mis-expression and default repression of genes, which might explain the pleiotropic phenotypes of the mutants.
利用单克隆抗体，我鉴定出了果蝇的一种核蛋白BJ1（分子量约为68kd），并分离出了其基因。生化分析表明，BJ1蛋白与核小体相关，并且如先前对高迁移率族蛋白（HMGs）所显示的那样，可被嵌入DNA的试剂从染色质中释放出来。在多线染色体上，该蛋白定位于所有条带，对特定基因座没有偏好。BJ1蛋白，尤其是BJ1 mRNA，在母体中强烈表达。在早期胚胎中，所有细胞核都含有等量的BJ1。在神经母细胞形成过程中，BJ1 mRNA局限于中枢神经系统的细胞，并且在该组织的细胞核中发现了更高水平的蛋白。在胚胎后期，mRNA几乎完全消失，但大量的BJ1蛋白一直持续到形态发生阶段。BJ1基因编码一个含有两种不同类型内部重复序列的547个氨基酸的多肽。从氨基酸46到417的序列包含七个第一种类型的重复序列，在进化过程中高度保守。该区域45%的氨基酸在人类染色质凝聚调节因子RCC1基因的七个相似串联重复序列中保守。携带RCC1突变的细胞系的表型表明该基因在细胞周期控制中起主要作用。一个酵母基因SRM1/PRP20也含有这些重复序列，并且在该区域与BJ1有30%的氨基酸同一性。该基因的突变扰乱mRNA代谢，破坏核结构，并改变交配信息素的信号转导途径。互补实验表明这些基因在不同物种中具有共同功能。我提出它们的基因产物与染色质结合以建立或维持适当的高级结构，作为调节基因表达的先决条件。这种结构的破坏可能导致基因的错误表达和默认抑制，这可能解释了突变体的多效性表型。
