Nakajima Y
Second Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Tokyo Medical and Dental University.
Kokubyo Gakkai Zasshi. 1998 Jun;65(2):172-88. doi: 10.5357/koubyou.65.172.
The E2F transcription factor plays an important role in controlling the expression of genes required for cell cycle progression. The transcription of a number of these genes, including E2F1 and B-myb, is repressed in G0/early G1 at E2F DNA binding sites mediated by interaction of E2F with the Rb family member proteins. It was shown that a corepressor element CHR, which was originally identified in the B-myb promoter, is also responsible for the repression of the E2F1 promoter. The mutation of the CHR element adjacent to E2F sites leads to a derepression of the E2F1 promoter in quiescent cells. The CHR-mutated promoter is activated by the E2F family of proteins (E2F1, E2F2, E2F3, and E2F4) but unable to be repressed by any of the Rb family members (Rb, p107, and p130) to the level of the wild-type promoter activity in G0, indicating that the repression by the Rb family members is required for the corepressor element. Moreover, it was shown that a factor specifically bound to the CHR element is co-purified with E2F by DNA affinity purification and co-immunoprecipitated with E2F4 and the Rb family members. These results seggested that E2F and the Rb family member proteins regulate the transcription of the E2F1 and B-myb genes by associating with an additional corepressor protein.
E2F转录因子在控制细胞周期进程所需基因的表达中发挥着重要作用。许多这类基因的转录,包括E2F1和B-myb,在G0/早期G1期,在由E2F与Rb家族成员蛋白相互作用介导的E2F DNA结合位点处受到抑制。研究表明,最初在B-myb启动子中鉴定出的共抑制因子元件CHR,也负责E2F1启动子的抑制。与E2F位点相邻的CHR元件发生突变,会导致静止细胞中E2F1启动子的去抑制。CHR突变的启动子被E2F家族蛋白(E2F1、E2F2、E2F3和E2F4)激活,但在G0期无法被任何Rb家族成员(Rb、p107和p130)抑制到野生型启动子活性水平,这表明Rb家族成员的抑制作用是共抑制因子元件所必需的。此外,研究表明,一种与CHR元件特异性结合的因子通过DNA亲和纯化与E2F共纯化,并与E2F4和Rb家族成员共免疫沉淀。这些结果表明,E2F和Rb家族成员蛋白通过与一种额外的共抑制蛋白结合来调节E2F1和B-myb基因的转录。