Critical role of the HMGI(Y) proteins in adipocytic cell growth and differentiation (Retracted article. See vol. 38, 2018)
Critical role of the HMGI(Y) proteins in adipocytic cell growth and differentiation (Retracted article. See vol. 38, 2018)
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DOI：
10.1128/mcb.21.7.2485-2495.2001
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发表时间：
2001-04-01
影响因子：
5.3
通讯作者：
Fusco, A
中科院分区：
文献类型：
--
作者：
Melillo, RM;Pierantoni, GM;Fusco, A
高迁移率 I 族 (HMGI) 非组蛋白染色体蛋白 HMGI(Y) 和 HMGI-C 与定义染色质结构和调节多个基因的转录有关。这些蛋白质与脂肪细胞稳态有关：在 HMGI-C 基因座有针对性破坏的小鼠中发现脂肪组织严重缺乏，而人类的脂肪瘤生成通常与 HMGI 基因的体细胞突变有关。本研究的目的是检查 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3T3-L1细胞系的分化引起HMGI(Y)基因表达的早期诱导。通过反义技术抑制 HMGI(Y) 表达可显着提高这些细胞的生长速度并损害脂肪细胞分化。脂肪形成分化过程涉及多种转录因子的相互作用，其中包括 CCAAT/增强子结合蛋白 (C/EBP) 蛋白家族。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的转录控制的假设。我们发现 HMGI(Y) 蛋白在体内和体外结合 C/EBP β。此外，我们发现 HMGI(Y) 强烈增强了 C/EBP beta 反式激活瘦素启动子（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) 蛋白在脂肪细胞生长和分化中发挥着关键作用。
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/EBP beta in vivo and in vitro. Furthermore, we show that HMGI(Y) strongly potentiates the capacity of C/EBP beta 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.