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延伸因子复合物的hELP3亚基调控人类细胞中HSP70基因的转录。

hELP3 subunit of the Elongator complex regulates the transcription of HSP70 gene in human cells.

作者信息

Han Qiuju, Hou Xiaozhe, Su Dongmei, Pan Lina, Duan Jizhou, Cui Liguo, Huang Baiqu, Lu Jun

机构信息

Institute of Genetics and Cytology, Northeast Normal University, Changchun 130024, China.

出版信息

Acta Biochim Biophys Sin (Shanghai). 2007 Jun;39(6):453-61. doi: 10.1111/j.1745-7270.2007.00293.x.

Abstract

The human Elongator complex is remarkably similar to its yeast counterpart in several aspects. In a previous study, we analyzed the functions of the human elongation protein 3 (hELP3) subunit of the human Elongator by using an in vivo yeast complementation system. However, direct evidence for hELP3 functions in regulating gene expression in human cells was not obtained. In this study, we used hELP3 antisense oligonucleotide inhibitors to knock down hELP3 gene expression to investigate its function in human 293T cells. The results showed that specific reduction of hELP3 mRNA and protein caused a significant suppression of HSP70-2 gene expression, and this was accompanied by histone H3 hypoacetylation and decreased RNA polymerase II density at the HSP70-2 gene. Moreover, the data also showed that hELP3 exerted the transcriptional regulatory function directly through its presence on the HSP70-2 gene. Data presented in this report provide further insight and direct evidence of the functions of hELP3 in HSP70-2 gene transcriptional elongation in human cells.

摘要

人类延伸因子复合物在几个方面与其酵母对应物极为相似。在先前的一项研究中,我们通过体内酵母互补系统分析了人类延伸因子复合物中人类延伸蛋白3(hELP3)亚基的功能。然而,并未获得hELP3在调节人类细胞基因表达中发挥功能的直接证据。在本研究中,我们使用hELP3反义寡核苷酸抑制剂敲低hELP3基因表达,以研究其在人类293T细胞中的功能。结果表明,hELP3 mRNA和蛋白的特异性减少导致HSP70-2基因表达显著受抑,同时伴随着组蛋白H3低乙酰化以及HSP70-2基因处RNA聚合酶II密度降低。此外,数据还表明,hELP3通过其在HSP70-2基因上的存在直接发挥转录调节功能。本报告中的数据为hELP3在人类细胞HSP70-2基因转录延伸中的功能提供了进一步的见解和直接证据。

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