Transcriptional regulation of human chromatin assembly factor ASF1
Transcriptional regulation of human chromatin assembly factor ASF1
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DOI：
10.1089/dna.2006.0515
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发表时间：
2007-02-01
影响因子：
3.1
通讯作者：
Yoshida, Kenichi
中科院分区：
文献类型：
--
作者：
Hayashi, Reiko;Goto, Yuya;Yoshida, Kenichi
抗沉默功能1（ASF1）是一种保守的组蛋白伴侣，参与核小体组装、转录沉默和细胞对DNA损伤的反应。在这里，我们报告的鉴定人ASF1B，而不是ASF1A，作为转录因子E2F1的直接转录靶。我们证明，E2F1过表达的腺病毒介导的基因转移上调ASF1B mRNA在HeLa细胞中的表达。对人ASF1B启动子构建体的分析表明，E2F响应序列是E2F1诱导的ASF1B基因转录激活所必需的。包括E2F共有序列的寡核苷酸在体外被E2F1蛋白特异性结合。染色质免疫沉淀分析表明，E2F1结合到人ASF1B基因的E2F响应序列。在E2F家族的成员中，E2F1至E2F5，而不是E2F6，激活了ASF1B报告基因构建体。Sp1和NFYA不能诱导ASF1A和ASF1B启动子的活性。血清刺激可上调ASF1A和ASF1B mRNA表达。综上所述，我们的结果表明，人ASF1A和ASF1B的表达上调后的细胞增殖信号，但ASF1B的独特调控转录因子E2F在细胞周期的进展。
Antisilencing function 1 ( ASF1) is a conserved histone chaperone implicated in nucleosome assembly, transcriptional silencing, and the cellular response to DNA damage. Here, we report the identification of human ASF1B, but not ASF1A, as a direct transcriptional target of transcription factor E2F1. We demonstrated that overexpression of E2F1 by adenoviral-mediated gene transfer upregulated ASF1B mRNA expression in HeLa cells. Analysis of human ASF1B promoter constructs showed that an E2F-responsive sequence was necessary for E2F1-induced activation of the ASF1B gene transcription. Oligonucleotides including an E2F consensus sequence were specifically bound by E2F1 protein in vitro. Chromatin immunoprecipitation analysis demonstrated that E2F1 bound to an E2F-responsive sequence of the human ASF1B gene. Among the members of the E2F family, E2F1 to E2F5, but not E2F6, activated the ASF1B reporter construct. Sp1 and NFYA failed to induce the activity of the ASF1A and ASF1B promoter. ASF1A and ASF1B mRNA were upregulated by serum stimulation. Taken together, our results suggest that the expression of human ASF1A and ASF1B are upregulated followed by cell proliferation signal, but that of ASF1B is uniquely regulated by transcription factors E2F during cell cycle progression.