Binding of NF-KB-like factors to regulatory sequences of the c-myc gene.
Binding of NF-KB-like factors to regulatory sequences of the c-myc gene.
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DOI：
10.1007/978-3-642-75889-8_27
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发表时间：
1990
影响因子：
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通讯作者：
M. Duyao;D. J. Kessler;D. Spicer;G. Sonenshein
中科院分区：
文献类型：
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作者：
M. Duyao;D. J. Kessler;D. Spicer;G. Sonenshein
在细胞对生长或分化的反应过程中，c-mycproto-oncogene表达的变化通常在转录水平上介导，包括对起始和延伸速率的控制。c-mycgene转录起始和延伸水平的调节可能是由特定蛋白质与基因附近或基因内的调节元件相互作用介导的。已鉴定出鼠c-myc基因的正调控元件和负调控元件（Remmers等，1986; Bentley和Groudine，1988）。为了阐明负调控c-myc转录的机制，我们采用韦姆231早期B淋巴瘤细胞系作为模型系统，因为在这些小鼠细胞中，c-myc基因表达调控的主要成分发生在转录水平。WEHI 231细胞的增殖可以在与针对所表达的表面IG的抗血清（例如山羊抗小鼠IG制剂（加米格））孵育后24-48小时内停止（McCormack et. 1984）或用佛波酯处理（Levine等1986）。先前我们证明了在处理的24小时内发生c-mycmRNA表达的选择性5至10倍降低;这种降低与c-mycgene转录的降低相关（Levine et. 1986）。我们推断，这种转录速率降低的控制可能与增加因子与负元件的结合或减少因子与正元件的结合有关。在任何一种情况下，约束力的变化都可能是显而易见的。在这里，我们报告的变化在复杂的相互作用的蛋白质在两个网站内的c-mycocus在生长停滞WEHI 231细胞中的c-mycgene转录下调期间的映射。介导这种结合的序列与NF-κ B因子家族内的蛋白质相互作用，暗示这些因子参与c-mycgene转录的调节。
Changes in expression of the c-mycproto-oncogene during the response of cells to growth or differentiation are often mediated at the transcriptional level, including control of the rates of initiation and elongation. Regulation of the level of initiation and elongation of c-mycgene transcription is likely to be mediated by the interaction of specific proteins with regulatory elements near or within the gene. Both positive and negative regulatory elements have been identified for the murine c-mycgene (Remmers et.al. 1986; Bentley and Groudine, 1988). To elucidate the mechanisms involved in negative control of c-myctranscription, we have employed the WEM 231 early B lymphoma cell line as a model system, since a major component of regulation of c-mycgene expression in these murine cells occurs at the level of transcription. Proliferation of WEHI 231 cells can be arrested within 24–48 hours following incubation with an antiserum against the expressed surface Ig, such as a goat anti-mouse Ig preparation (GaMIg) (McCormack et. al. 1984) or by treatment with phorbol ester (Levine et.al. 1986). Previously we demonstrated that a selective 5- to 10- fold decrease in c-mycmRNA expression occurs within 24 hours of treatment; this drop correlated with a decrease in the transcription of the c-mycgene (Levine et. al. 1986). We reasoned that control of this decreased rate of transcription could relate either to increased factor binding to a negative element or decreased binding to a positive element. In either case, a change in binding might be apparent. Here we report on the mapping of changes in the complex interaction of proteins at two sites within the c-myclocus during the down modulation of c-mycgene transcription in growth arrested WEHI 231 cells. The sequences mediating this binding are interacting with proteins within the NF-KB family of factors, implicating these factors in the regulation of c-mycgene transcription.