核心启动子因子TAF9B调节神经元基因表达。
Core promoter factor TAF9B regulates neuronal gene expression.
作者信息
Herrera Francisco J, Yamaguchi Teppei, Roelink Henk, Tjian Robert
机构信息
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States CIRM Center of Excellence, Li Ka Shing Center For Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States CIRM Center of Excellence, Li Ka Shing Center For Biomedical and Health Sciences, University of California, Berkeley, Berkeley, United States.
出版信息
Elife. 2014 Jul 8;3:e02559. doi: 10.7554/eLife.02559.
Emerging evidence points to an unexpected diversification of core promoter recognition complexes that serve as important regulators of cell-type specific gene transcription. Here, we report that the orphan TBP-associated factor TAF9B is selectively up-regulated upon in vitro motor neuron differentiation, and is required for the transcriptional induction of specific neuronal genes, while dispensable for global gene expression in murine ES cells. TAF9B binds to both promoters and distal enhancers of neuronal genes, partially co-localizing at binding sites of OLIG2, a key activator of motor neuron differentiation. Surprisingly, in this neuronal context TAF9B becomes preferentially associated with PCAF rather than the canonical TFIID complex. Analysis of dissected spinal column from Taf9b KO mice confirmed that TAF9B also regulates neuronal gene transcription in vivo. Our findings suggest that alternative core promoter complexes may provide a key mechanism to lock in and maintain specific transcriptional programs in terminally differentiated cell types.DOI: http://dx.doi.org/10.7554/eLife.02559.001.
新出现的证据表明，作为细胞类型特异性基因转录重要调节因子的核心启动子识别复合物存在意想不到的多样性。在此，我们报告孤儿TBP相关因子TAF9B在体外运动神经元分化时被选择性上调，并且是特定神经元基因转录诱导所必需的，而对于小鼠胚胎干细胞中的全局基因表达则是可有可无的。TAF9B与神经元基因的启动子和远端增强子都结合，部分共定位于运动神经元分化的关键激活因子OLIG2的结合位点。令人惊讶的是，在这种神经元环境中，TAF9B优先与PCAF而非经典的TFIID复合物相关联。对Taf9b基因敲除小鼠的解剖脊柱分析证实，TAF9B在体内也调节神经元基因转录。我们的研究结果表明，替代核心启动子复合物可能提供一种关键机制，以锁定并维持终末分化细胞类型中的特定转录程序。DOI: http://dx.doi.org/10.7554/eLife.02559.001 。
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