Bruggeman Sophia W M, Valk-Lingbeek Merel E, van der Stoop Petra P M, Jacobs Jacqueline J L, Kieboom Karin, Tanger Ellen, Hulsman Danielle, Leung Carly, Arsenijevic Yvan, Marino Silvia, van Lohuizen Maarten
Division of Molecular Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Genes Dev. 2005 Jun 15;19(12):1438-43. doi: 10.1101/gad.1299305.
The Polycomb group (PcG) gene Bmi1 promotes cell proliferation and stem cell self-renewal by repressing the Ink4a/Arf locus. We used a genetic approach to investigate whether Ink4a or Arf is more critical for relaying Bmi1 function in lymphoid cells, neural progenitors, and neural stem cells. We show that Arf is a general target of Bmi1, however particularly in neural stem cells, derepression of Ink4a contributes to Bmi1(-/-) phenotypes. Additionally, we demonstrate haploinsufficient effects for the Ink4a/Arf locus downstream of Bmi1 in vivo. This suggests differential, cell type-specific roles for Ink4a versus Arf in PcG-mediated (stem) cell cycle control.
多梳蛋白家族（PcG）基因Bmi1通过抑制Ink4a/Arf基因座来促进细胞增殖和干细胞自我更新。我们采用遗传学方法研究Ink4a或Arf在淋巴细胞、神经祖细胞和神经干细胞中传递Bmi1功能方面是否更为关键。我们发现Arf是Bmi1的一个普遍靶点，然而特别是在神经干细胞中，Ink4a的去抑制作用导致了Bmi1基因敲除小鼠的表型。此外，我们在体内证明了Bmi1下游的Ink4a/Arf基因座存在单倍剂量不足效应。这表明在PcG介导的（干）细胞周期调控中，Ink4a和Arf具有不同的、细胞类型特异性的作用。
