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首页> 外文期刊>Molecular and Cellular Biology >Critical Role of the HMGI(Y) Proteins in Adipocytic Cell Growth and Differentiation
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Critical Role of the HMGI(Y) Proteins in Adipocytic Cell Growth and Differentiation

机译：HMGI（Y）蛋白在脂肪细胞生长和分化中的关键作用

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The high-mobility group I (HMGI) nonhistone chromosomal proteins HMGI(Y) and HMGI-C have been implicated in defining chromatin structure and in regulating the transcription of several genes. These proteins have been implicated in adipocyte homeostasis: a severe deficiency of fat tissue is found in mice with targeted disruption of the HMGI-C locus, and lipomagenesis in humans is frequently associated with somatic mutations of HMGI genes. The aim of this study was to examine the role of HMGI(Y) proteins in adipocytic cell growth and differentiation. First, we found that differentiation of the preadipocytic 3T3-L1 cell line caused early induction of HMGI(Y) gene expression. Suppression of HMGI(Y) expression by antisense technology dramatically increased the growth rate and impaired adipocytic differentiation in these cells. The process of adipogenic differentiation involves the interplay of several transcription factors, among which is the CCAAT/enhancer-binding protein (C/EBP) family of proteins. These factors are required for the transcriptional activation of adipocyte-specific genes. We also tested the hypothesis that HMGI(Y) might participate in transcriptional control of adipocyte-specific promoters. We found that HMGI(Y) proteins bind C/EBPβ in vivo and in vitro. Furthermore, we show that HMGI(Y) strongly potentiates the capacity of C/EBPβ to transactivate the leptin promoter, an adipose-specific promoter. Taken together, these results indicate that the HMGI(Y) proteins play a critical role in adipocytic cell growth and differentiation.
机译：高迁移率的I组（HMGI）非组蛋白染色体蛋白HMGI（Y）和HMGI-C与确定染色质结构和调节几个基因的转录有关。这些蛋白质与脂肪细胞的动态平衡有关：在有针对性破坏HMGI-C基因座的小鼠中发现了脂肪组织的严重缺乏，并且人类的脂肪形成通常与HMGI基因的体细胞突变有关。这项研究的目的是检查HMGI（Y）蛋白在脂肪细胞生长和分化中的作用。首先，我们发现前脂肪细胞的3T3-L1细胞系的分化引起了HMGI（Y）基因表达的早期诱导。通过反义技术抑制HMGI（Y）的表达大大增加了这些细胞的生长速率并损害了脂肪细胞的分化。成脂分化过程涉及多个转录因子的相互作用，其中包括CCAAT /增强子结合蛋白（C / EBP）家族。这些因子是脂肪细胞特异性基因转录激活所必需的。我们还测试了HMGI（Y）可能参与脂肪细胞特异性启动子转录控制的假设。我们发现HMGI（Y）蛋白在体内和体外结合C /EBPβ。此外，我们表明HMGI（Y）强烈增强了C /EBPβ激活瘦素启动子（一种脂肪特异性启动子）的能力。综上所述，这些结果表明HMGI（Y）蛋白在脂肪细胞的生长和分化中起关键作用。

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