Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development
Roles of VWRPY motif-mediated gene repression by Runx proteins during T-cell development
复制标题
DOI：
10.1038/icb.2012.6
复制
发表时间：
2012-09-01
影响因子：
4
通讯作者：
Taniuchi, Ichiro
中科院分区：
文献类型：
--
作者：
Seo, Wooseok;Tanaka, Hirokazu;Taniuchi, Ichiro
Runx转录因子家族蛋白通过激活或抑制靶基因在t细胞发育过程中发挥重要作用。例如，Cd4和ThPOK的谱系和阶段特异性表达由嵌入每个位点的转录沉默子控制，其活性需要结合Runx复合物。Runx蛋白中进化保守的VWRPY五肽序列作为募集Groucho/TLE转录共阻遏子的平台，已被证明具有抑制功能。然而，Runx靶基因对VWRPY基序的需求是否不同尚不清楚。通过检测Runx1和Runx3蛋白中缺乏VWRPY基序的小鼠，我们在cd8谱系T细胞中分别显示了Cd4和ThPOK的完全和部分下调。因此，尽管Cd4沉默完全依赖于VWRPY基序，但VWRPY依赖性和非依赖性机制都可以抑制ThPOK基因。这些结果表明Runx蛋白利用不同的模式抑制不同靶基因的表达。免疫学与细胞生物学（2012）90,827-830；doi: 10.1038 / icb.2012.6;2012年2月28日在线发布
Runx transcription factor family proteins have essential roles during T-cell development by either activating or repressing target genes. For instance, lineage-and stage-specific expression of Cd4 and ThPOK is controlled by a transcriptional silencer embedded in each locus, whose activity requires bindings of Runx complexes. The evolutionarily conserved VWRPY pentapeptide sequences in Runx proteins have been shown to be responsible for repressive function as a platform to recruit Groucho/TLE transcriptional corepressors. However, it remains elusive whether requirement for the VWRPY motif differs among Runx target genes. By examining mice lacking VWRPY motifs in both Runx1 and Runx3 proteins, here, we show a full and partial derepression of Cd4 and ThPOK in CD8-linegae T cells, respectively. Thus, whereas Cd4 silencing completely depends on the VWRPY motif, both VWRPY-dependent and -independent mechanisms operate to repress ThPOK gene. These results indicate that Runx proteins utilize different modes to repress expression of different target genes. Immunology and Cell Biology (2012) 90, 827-830; doi:10.1038/icb.2012.6; published online 28 February 2012