胰岛素结合蛋白(IBPs)通过与特定的DNA位点结合以促进适当的基因调控,在调节基因表达中起着重要作用。果蝇中有几个IBP,每个定义为它们在转基因测定中使靶基因启动子与相邻调控元件的激活或沉默效应隔离的能力。其中,只有CCCTC结合因子(CTCF)在哺乳动物中具有明显的直系同源。CTCF对于哺乳动物细胞活力是必需的,并且是基因组结构的重要调节因子。在苍蝇中,CTCF既是母体保藏的,也是合子表达的。缺乏合子CTCF的苍蝇死于患有同种异体缺陷的年轻成年人,这表明特定的Hox基因在不适当的身体片段中被错误表达。缺乏任何主要的胚胎缺陷被认为是由于母体供应CTCF蛋白,由于母体贡献的因素通常足以通过许多胚胎发生进行。这里,我们最终确定了果蝇发育进展对CTCF的需求我们产生了完全缺乏母体和合子CTCF的动物,并发现,与预期相反,这些突变体通过胚胎发生和幼虫生命来发展。它们发展成成年人,他们没能从p的案子中解脱出来。与合子突变体相比,这些突变体显示出加剧的同源缺陷,在发育早期错误表达Hox基因Abdominal-B在其正常表达域之外。我们的结果表明,果蝇CTCF的缺失并不伴随着对基因表达的广泛影响,这可能是由于其他IBP的冗余功能。相反,CTCF对于正确的Hox基因表达模式和成年果蝇的生存能力是必需的。
Insulator binding proteins (IBPs) play an important role in regulating gene expression by binding to specific DNA sites to facilitate appropriate gene regulation. There are several IBPs in Drosophila, each defined by their ability to insulate target gene promoters in transgenic assays from the activating or silencing effects of neighboring regulatory elements. Of these, only CCCTC-binding factor (CTCF) has an obvious ortholog in mammals. CTCF is essential for mammalian cell viability and is an important regulator of genome architecture. In flies, CTCF is both maternally deposited and zygotically expressed. Flies lacking zygotic CTCF die as young adults with homeotic defects, suggesting that specific Hox genes are misexpressed in inappropriate body segments. The lack of any major embryonic defects was assumed to be due to the maternal supply of CTCF protein, as maternally contributed factors are often sufficient to progress through much of embryogenesis. Here, we definitively determined the requirement of CTCF for developmental progression in Drosophila We generated animals that completely lack both maternal and zygotic CTCF and found that, contrary to expectation, these mutants progress through embryogenesis and larval life. They develop to pharate adults, which fail to eclose from their pupal case. These mutants show exacerbated homeotic defects compared to zygotic mutants, misexpressing the Hox gene Abdominal-B outside of its normal expression domain early in development. Our results indicate that loss of Drosophila CTCF is not accompanied by widespread effects on gene expression, which may be due to redundant functions with other IBPs. Rather, CTCF is required for correct Hox gene expression patterns and for the viability of adult Drosophila.