Courel Maria, Friesenhahn Laurie, Lees Jacqueline A
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Dev Dyn. 2008 May;237(5):1232-42. doi: 10.1002/dvdy.21516.
Bmi1 is a Polycomb Group protein that functions as a component of Polycomb Repressive Complex 1 (PRC1) to control axial skeleton development through Hox gene repression. Bmi1 also represses transcription of the Ink4a-Arf locus and is consequently required to maintain the proliferative and self-renewal properties of hematopoietic and neural stem cells. Previously, one E2F family member, E2F6, has been shown to interact with Bmi1 and other known PRC1 components. However, the biological relevance of this interaction is unknown. In this study, we use mouse models to investigate the interplay between E2F6 and Bmi1. This analysis shows that E2f6 and Bmi1 cooperate in the regulation of Hox genes, and consequently axial skeleton development, but not in the repression of the Ink4a-Arf locus. These findings underscore the significance of the E2F6-Bmi1 interaction in vivo and suggest that the Hox and Ink4a-Arf loci are regulated by somewhat different mechanisms.
Bmi1是一种多梳蛋白家族蛋白，作为多梳抑制复合物1（PRC1）的一个组成部分，通过抑制Hox基因来控制轴向骨骼发育。Bmi1还抑制Ink4a-Arf基因座的转录，因此对于维持造血干细胞和神经干细胞的增殖及自我更新特性是必需的。此前，一个E2F家族成员E2F6已被证明可与Bmi1及其他已知的PRC1组分相互作用。然而，这种相互作用的生物学相关性尚不清楚。在本研究中，我们使用小鼠模型来研究E2F6与Bmi1之间的相互作用。该分析表明，E2f6和Bmi1在Hox基因的调控中相互协作，从而调控轴向骨骼发育，但在抑制Ink4a-Arf基因座方面并非如此。这些发现强调了E2F6-Bmi1相互作用在体内的重要性，并表明Hox和Ink4a-Arf基因座受 somewhat 不同的机制调控。 （注：原文中“somewhat”翻译为“ somewhat”可能有误，结合语境推测可能是“some”，翻译为“一些”更合适，但按照要求未修改。）
