Myc induces the nucleolin and BN51 genes: possible implications in ribosome biogenesis
Myc induces the nucleolin and BN51 genes: possible implications in ribosome biogenesis
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DOI：
10.1093/nar/28.2.446
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发表时间：
2000-01-15
影响因子：
14.9
通讯作者：
Amati, B
中科院分区：
文献类型：
--
作者：
Greasley, PJ;Bonnard, C;Amati, B
c - Myc癌蛋白及其二聚化伙伴Max结合DNA核心共有序列CACGTG（E - 盒）并激活基因转录。然而，诱导水平较低阻碍了通过差异筛选技术鉴定新的Myc靶基因。在此，我们描述了一种基于计算机对候选Myc/Max靶基因的预选，基于两个限制性标准：Myc/Max结合的扩展E - 盒共有序列以及该序列在潜在基因组CpG岛中的出现。通过这些标准选择的候选基因通过实验评估其对Myc的反应。这里详细描述了两个Myc靶基因。它们分别编码核仁素（一种丰富的核仁蛋白）和BN51（一种RNA聚合酶III的辅因子）。Myc通过位于它们第一个内含子中的E - 盒激活这两个基因的转录，正如对几个已充分表征的Myc靶基因所观察到的那样。对于这两个基因，E - 盒的突变消除了Myc的转录激活以及Mad1的抑制作用。此外，BN51启动子被Myc选择性激活，而不被另一个E - 盒结合因子USF激活。核仁素和BN51都与核糖体RNA的成熟有关，尽管方式不同。我们提出，Myc通过对这些以及可能许多其他转录靶标的调控，可能是核糖体生物发生的一个重要调节因子。
The c-Myc oncoprotein and its dimerization partner Max bind the DNA core consensus sequence CACGTG (E-box) and activate gene transcription. However, the low levels of induction have hindered the identification of novel Myc target genes by differential screening techniques, Here, we describe a computer-based pre-selection of candidate Myc/Max target genes, based on two restrictive criteria: an extended E-box consensus sequence for Myc/Max binding and the occurrence of this sequence within a potential genomic CpG island. Candidate genes selected by these criteria were evaluated experimentally for their response to Myc. Two Myc target genes are characterized here in detail. These encode nucleolin, an abundant nucleolar protein, and BN51, a co-factor of RNA polymerase III. Myc activates transcription of both genes via E-boxes located in their first introns, as seen for several well-characterized Myc targets, For both genes, mutation of the E-boxes abolishes transcriptional activation by Myc as well as repression by Mad1. In addition, the BN51 promoter is selectively activated by Myc and not by USF, another E-box-binding factor, Both nucleolin and BN51 are implicated in the maturation of ribosomal RNAs, albeit in different ways. We propose that Myc, via regulation of these and probably many other transcriptional targets, may be an important regulator of ribosome biogenesis.