The Insulator Protein CTCF Is Required for Correct Hox Gene Expression, but Not for Embryonic Development in Drosophila.
The Insulator Protein CTCF Is Required for Correct Hox Gene Expression, but Not for Embryonic Development in Drosophila.
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DOI：
10.1534/genetics.118.301350
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发表时间：
2018-09
期刊：
影响因子：
3.3
通讯作者：
Furlong EEM
中科院分区：
文献类型：
--
作者：
Gambetta MC;Furlong EEM
绝缘子结合蛋白（Insulator binding proteins，IBPs）通过与特定的DNA位点结合，促进基因的适当调控，在基因表达调控中发挥重要作用。在果蝇中存在几种IBP，每种IBP都通过其在转基因测定中将靶基因启动子与邻近调节元件的激活或沉默效应隔离的能力来定义。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物。CTCF是哺乳动物细胞活力所必需的，并且是基因组结构的重要调节剂。在果蝇中，CTCF是母系沉积和合子表达。缺乏合子CTCF的果蝇在年轻时死于同源异型缺陷，这表明特定的Hox基因在不适当的身体片段中错误表达。没有任何主要的胚胎缺陷被认为是由于CTCF蛋白的母体供应，因为母体贡献的因素通常足以在大部分胚胎发生中进展。在这里，我们明确地确定了果蝇发育过程中CTCF的需求。我们产生的动物，完全缺乏母亲和合子CTCF，并发现，与预期相反，这些突变体的进展，通过胚胎发生和幼虫的生活。它们发育成pharate成人，不能从蛹壳中羽化。与合子突变体相比，这些突变体显示出加剧的同源异型缺陷，在发育早期在其正常表达域之外错误表达Hox基因Abdominal-B。我们的研究结果表明，果蝇CTCF的损失并不伴随着基因表达的广泛影响，这可能是由于冗余功能与其他IBP。相反，CTCF是正确的Hox基因表达模式和成年果蝇的生存能力所必需的。
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.
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