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首页> 外文期刊>Molecular and Cellular Biology >p300-Dependent Acetylation of Activating Transcription Factor 5 Enhances C/EBPβ Transactivation of C/EBPα during 3T3-L1 Differentiation
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p300-Dependent Acetylation of Activating Transcription Factor 5 Enhances C/EBPβ Transactivation of C/EBPα during 3T3-L1 Differentiation

机译：p300依赖性转录因子活化转录因子5增强3T3-L1分化过程中C /EBPα的C /EBPβ反式激活

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摘要

Adipogenesis is a multistep process by which 3T3-L1 preadipocytes differentiate into mature adipocytes through mitotic clonal expansion (MCE) and terminal differentiation. The CCAAT/enhancer-binding protein β (C/EBPβ) is an important transcription factor that takes part in both of these processes. C/EBPβ not only transactivates C/EBPα and the peroxisome proliferator-activated receptor γ (PPARγ), which cause 3T3-L1 preadipocytes to enter terminal adipocyte differentiation, but also is required to activate cell cycle genes necessary for MCE. The identification of potential cofactors of C/EBPβ will help to explain how C/EBPβ undertakes these specialized roles during the different stages of adipogenesis. In this study, we found that activating transcription factor 5 (ATF5) can bind to the promoter of C/EBPα via its direct interaction with C/EBPβ (which is mediated via the p300-dependent acetylation of ATF5), leading to enhanced C/EBPβ transactivation of C/EBPα. We also show that p300 is important for the interaction of ATF5 with C/EBPβ as well as for the binding activity of this complex on the C/EBPα promoter. Consistent with these findings, overexpression of ATF5 and an acetylated ATF5 mimic both promoted 3T3-L1 adipocyte differentiation, whereas short interfering RNA-mediated ATF5 downregulation inhibited this process. Furthermore, we show that the elevated expression of ATF5 is correlated with an obese phenotype in both mice and humans. In summary, we have identified ATF5 as a new cofactor of C/EBPβ and examined how C/EBPβ and ATF5 (acetylated by a p300-dependent mechanism) regulate the transcription of C/EBPα.
机译：脂肪生成是一个多步骤过程，通过该过程，3T3-L1前脂肪细胞通过有丝分裂克隆扩增（MCE）和终末分化而分化为成熟的脂肪细胞。 CCAAT /增强子结合蛋白β（C /EBPβ）是参与这两个过程的重要转录因子。 C /EBPβ不仅能使C /EBPα和过氧化物酶体增殖物激活的受体γ（PPARγ）活化，从而使3T3-L1前脂肪细胞进入末端脂肪细胞分化，而且还需要激活MCE必需的细胞周期基因。 C /EBPβ潜在辅因子的鉴定将有助于解释C /EBPβ在脂肪形成的不同阶段如何承担这些特殊的作用。在这项研究中，我们发现激活转录因子5（ATF5）可以通过与C /EBPβ的直接相互作用（通过ATF5的p300依赖性乙酰化介导）与C /EBPα的启动子结合，从而导致C / E增强C /EBPα的EBPβ反式激活。我们还显示p300对于ATF5与C /EBPβ的相互作用以及该复合物在C /EBPα启动子上的结合活性很重要。与这些发现一致的是，ATF5的过表达和乙酰化的ATF5模拟物都促进了3T3-L1脂肪细胞的分化，而短时干扰RNA介导的ATF5下调抑制了这一过程。此外，我们表明，在小鼠和人类中，ATF5的表达升高与肥胖表型有关。总之，我们已经将ATF5鉴定为C /EBPβ的新辅助因子，并研究了C /EBPβ和ATF5（通过p300依赖性机制被乙酰化）如何调节C /EBPα的转录。

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