The E2F6 transcription factor is a component of the mammalian Bmi1-containing polycomb complex

The E2F transcription factors play a key role in the regulation of cellular proliferation and terminal differentiation. E2F6 is the most recently identified and the least well understood member of the E2F family. It is only distantly related to the other E2Fs and lacks the sequences responsible for both transactivation and binding to the retinoblastoma protein. Consistent with this finding, E2F6 can behave as a dominant negative inhibitor of the other E2F family members. In this study, we continue to investigate the possible role(s) of E2F6 in vivo. We report the isolation of RYBP, a recently identified member of the mammalian polycomb complex, as an E2F6-interacting protein. Mapping studies indicate that RYBP binds within the known “repression domain” of E2F6. Moreover, we demonstrate that endogenous E2F6 and polycomb group proteins, including RYBP, Ring1, MEL-18, mph1, and the oncoprotein Bmi1, associate with one another. These findings suggest that the biological properties of E2F6 are mediated through its ability to recruit the polycomb transcriptional repressor complex.

E2F转录因子（E2F transcription factors）在细胞增殖与终末分化的调控中发挥关键作用。E2F6是E2F家族中最晚被鉴定、研究最不充分的成员。它与其他E2F家族成员亲缘关系甚远，且缺乏介导反式激活以及与视网膜母细胞瘤蛋白（retinoblastoma protein）结合的序列。与此发现一致，E2F6可作为其他E2F家族成员的显性负性抑制剂。本研究进一步探究了E2F6在体内的潜在功能。我们成功分离得到RYBP——一种新近鉴定的哺乳动物多梳复合体（polycomb complex）成员——作为E2F6的互作蛋白。定位分析显示，RYBP结合于E2F6已知的“抑制结构域”内。此外，我们证实内源性E2F6与多梳家族蛋白（包括RYBP、Ring1、MEL-18、mph1以及癌蛋白Bmi1）可相互结合。上述结果表明，E2F6的生物学特性是通过其招募多梳转录抑制复合体的能力实现的。