Distinct cellular factors regulate the c-myb promoter through its E2F element.
Distinct cellular factors regulate the c-myb promoter through its E2F element.
复制标题
不同的细胞因子通过其 E2F 元件调节 c-myb 启动子。
DOI：
10.1128/mcb.19.12.8442
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发表时间：
1999
影响因子：
5.3
通讯作者：
Flemington,E
中科院分区：
文献类型：
--
作者：
Campanero,MR;Armstrong,M;Flemington,E
大多数E2 F驱动的启动子在G1/S转换附近瞬时激活。虽然c-myb原癌基因的启动子含有E2 F元件，但它在进入细胞周期后的G1早期被诱导。此外，该启动子在随后的细胞周期中保持活性。由于E2 F位点在G1期作为阻遏物元件发挥作用（由于pRb与E2 F因子的关联），我们研究了c-myb启动子中的E2 F元件是否与G1期被阻遏的启动子中的E2 F元件不同。通过凝胶位移分析，发现来自c-myb启动子的E2 F元件形成独特的复合物，称为E2 Fmyb-sp，这在来自其他几个启动子的E2 F元件中没有观察到。DP-1、E2 F1 to-5、p107或pRb的抗体未能超转移或阻断E2 Fmyb-sp复合物的形成。甲基化干扰实验表明，E2 Fmyb-sp复合物的DNA接触残基与E2 F蛋白结合所需的残基不同，但重叠。除了鉴定E2 Fmyb-sp之外，我们还发现SP-1与c-mybE 2F元件结合。功能研究表明，E2 Fmyb-sp和/或SP-1是实现c-myb启动子在不同类型的细胞中的完全激活所必需的，并且在NIH 3 T3细胞中维持c-myb启动子在G1期的高表达。这些研究表明，E2 F元件可以通过独特的蛋白质组的结合进行不同的调节。
Most E2F-driven promoters are transiently activated around the G1/S transition. Although the promoter for the c-mybproto-oncogene harbors an E2F element, it is induced early in G1following entry into the cell cycle. Furthermore, this promoter remains active throughout subsequent cell cycles. Since E2F sites function as repressor elements during G1(due to the association of pRb with E2F factors), we investigated whether the E2F element in the c-mybpromoter is regulated differently than E2F elements in promoters that are repressed during G1. By gel shift analysis, the E2F element from the c-mybpromoter was found to form a unique complex, referred to as E2Fmyb-sp, which was not observed with E2F elements from several other promoters. Antibodies to DP-1, E2F1 to -5, p107, or pRb failed to either supershift or block E2Fmyb-sp complex formation. Methylation interference experiments indicate that the DNA contact residues for the E2Fmyb-sp complex are distinct from but overlapping with residues required for the binding of E2F proteins. In addition to the identification of E2Fmyb-sp, we have found that SP-1 binds to the c-mybE2F element. Functional studies revealed that E2Fmyb-sp and/or SP-1 are required to achieve full activation of the c-mybpromoter in different cell types and to maintain elevated expression of the c-mybpromoter during G1in NIH 3T3 cells. These studies demonstrate that E2F elements can be regulated differently through the binding of unique sets of proteins.