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首页> 外文期刊>Journal of cellular biochemistry. >The nuclear localization of WAP and CSN genes is modified by lactogenic hormones in HC11 cells.
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The nuclear localization of WAP and CSN genes is modified by lactogenic hormones in HC11 cells.

机译:WAP和CSN基因的核定位被HC11细胞中的生乳激素所修饰。

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Whey acidic protein (WAP) and casein (CSN) genes are among the most highly expressed milk protein genes in the mammary gland of the lactating mouse. Their tissue-specific regulation depends on the activation and recruitment of transcription factors, and chromatin modifications in response to hormonal stimulation. We have investigated if another mechanism, such as specific positioning of the genes in the nucleus, could be involved in their functional regulation. Fluorescent in situ hybridization was used to study the nuclear localization of WAP and CSN genes in mouse mammary epithelial cells (HC11) cultured in the absence and presence of lactogenic hormones. Automatic 3D image processing and analysis tools were developed to score gene positions. In the absence of lactogenic hormones, both genes are distributed non-uniformly within the nucleus: the CSN locus was located close to the nuclear periphery and the WAP gene tended to be central. Stimulation by lactogenic hormones induced a statistically significant change to their distance from the periphery, which has been described as a repressive compartment. The detection of genes in combination with the corresponding chromosome-specific probe revealed that the CSN locus is relocated outside its chromosome territory following hormonal stimulation, whereas the WAP gene, which is already sited more frequently outside its chromosome territory in the absence of hormones, is not affected. We conclude that milk protein genes are subject to nuclear repositioning when activated, in agreement with a role for nuclear architecture in gene regulation, but that they behave differently as a function of their chromosomal context.
机译:乳清酸性蛋白(WAP)和酪蛋白(CSN)基因是泌乳小鼠乳腺中表达最强的牛奶蛋白基因之一。它们的组织特异性调节取决于转录因子的激活和募集以及响应激素刺激的染色质修饰。我们已经研究了另一种机制,例如基因在细胞核中的特定定位,是否可以参与其功能调节。荧光原位杂交用于研究在不存在和存在乳原激素的情况下培养的小鼠乳腺上皮细胞(HC11)中WAP和CSN基因的核定位。开发了自动3D图像处理和分析工具来对基因位置进行评分。在缺乏生乳激素的情况下,两个基因均不均匀地分布在细胞核内:CSN基因座位于靠近核外围的位置,WAP基因倾向于处于中心位置。泌乳激素的刺激导致它们与周围的距离发生统计学上的显着变化,这已被描述为抑制隔室。对基因的检测以及相应的染色体特异性探针的发现表明,在激素刺激下,CSN基因位点位于其染色体区域之外,而在没有激素的情况下,WAP基因已经更加频繁地位于其染色体区域之外。不受影响。我们得出的结论是,乳蛋白基因在被激活时会受到核的重新定位,这与核结构在基因调控中的作用相一致,但是它们作为染色体背景的功能却表现不同。

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