A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells
A Lin-9 complex is recruited by B-Myb to activate transcription of G2/M genes in undifferentiated embryonal carcinoma cells
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DOI：
10.1038/onc.2009.22
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发表时间：
2009-04-16
期刊：
影响因子：
8
通讯作者：
Watson, R. J.
中科院分区：
文献类型：
--
作者：
Knight, A. S.;Notaridou, M.;Watson, R. J.
最近发现，细胞周期基因的转录受一个名为LINC的核心复合体的调控，该复合体从G(0)-G(1)中与p130或p107口袋蛋白和E2F4的转录抑制复合体切换到S-G(2)中包含B-Myb的转录活性复合体。我们研究了LINC在F9胚胎癌细胞中的功能，F9胚胎癌细胞的特点是极短的G(1)期导致了快速的细胞周期。我们发现在F9细胞中抑制LINC成分LIN-9的表达会导致有丝分裂停滞，我们已经使用这个系统来筛选转录靶标。在这些细胞中，B-Myb存在于与LIN-9和其他几种LINC成分的复合体中，但除非F9细胞分化，否则口袋蛋白不与LINC结合。Cyclin B1、Survivin等G(2)/M基因转录均需要LIN-9和B-Myb。此外，B-Myb通过多个Myb结合位点将Lin-9募集到Survivin启动子上。在缺乏G(1)/S检查点的细胞中，B-Myb/LINC复合体在有丝分裂过程中是至关重要的，这一证明对未分化的胚胎细胞和口袋蛋白功能受损的癌症都有意义。
It has recently been discovered that cell-cycle gene transcription is regulated by a core complex named LINC that switches from a transcriptionally repressive complex in G(0)-G(1) with the p130 or p107 pocket proteins and E2F4 to a transcriptionally active complex in S-G(2) containing B-Myb. We have studied the function of LINC in F9 embryonal carcinoma cells, which are distinguished by a rapid cell cycle resulting from an extremely short G(1) phase. We show that suppressing expression of the LINC component, Lin-9, in F9 cells causes arrest in mitosis, and we have used this system to screen for transcriptional targets. In these cells, B-Myb was found in complexes with Lin-9 and several other LINC constituents, however, the pocket proteins did not associate with LINC unless F9 cells were differentiated. Lin-9 and B-Myb were both required for transcription of G(2)/M genes such as Cyclin B1 and Survivin. Moreover, B-Myb was demonstrated to recruit Lin-9 to the Survivin promoter through multiple Myb-binding sites. The demonstration that a B-Myb/LINC complex is vital for progression through mitosis in cells lacking a G(1)/S checkpoint has implications for both undifferentiated embryonal cells and for cancers in which pocket protein function is compromised.