Centro Nacional de Biotecnología-CSIC, Cantoblanco, 28049 Madrid, Spain.
Curr Biol. 2011 Jun 21;21(12):999-1008. doi: 10.1016/j.cub.2011.04.041. Epub 2011 May 27.
The onset of differentiation entails modifying the gene expression state of cells, to allow activation of developmental programs that are maintained repressed in the undifferentiated precursor cells [1, 2]. This requires a mechanism to change gene expression on a genome-scale. Recent evidence suggests that in mammalian stem cells, derepression of developmental regulators during differentiation involves a shift from stalled to productive elongation of their transcripts [3-5], but factors mediating this shift have not been identified and the evidence remains correlative.
We report the identification of the MINIYO (IYO) gene, a positive regulator of transcriptional elongation that is essential for cells to initiate differentiation in Arabidopsis. IYO interacts with RNA polymerase II and the Elongator complex and is required to sustain global levels of transcriptional elongation activity, specifically in differentiating tissues. Accordingly, IYO is expressed in embryos, meristems, and organ primordia and not in mature tissues. Moreover, differential subcellular protein distribution further refines the domain of IYO function by directing nuclear accumulation, and thus its transcriptional activity, to cells initiating differentiation. Importantly, IYO overexpression induces premature cell differentiation and leads to meristem termination phenotypes.
These findings identify IYO as a necessary and sufficient factor for initiating differentiation in Arabidopsis and suggest that the targeted nuclear accumulation of IYO functions as a transcriptional switch for this fate transition.
分化的起始需要改变细胞的基因表达状态,以激活在未分化前体细胞中被抑制的发育程序[1,2]。这需要一种在全基因组范围内改变基因表达的机制。最近的证据表明,在哺乳动物干细胞中,分化过程中发育调控因子的去抑制涉及到它们转录本的从停滞到有生产力的延伸的转变[3-5],但介导这种转变的因素尚未被鉴定,并且证据仍然是相关的。
我们报告了 MINIYO(IYO)基因的鉴定,它是一个转录延伸的正调控因子,对拟南芥细胞开始分化是必不可少的。IYO 与 RNA 聚合酶 II 和 Elongator 复合物相互作用,并且需要维持转录延伸活性的整体水平,特别是在分化组织中。因此,IYO 在胚胎、分生组织和器官原基中表达,而不在成熟组织中表达。此外,差异的亚细胞蛋白分布通过指导核积累,从而指导其转录活性,进一步细化了 IYO 功能的域,以指向开始分化的细胞。重要的是,IYO 的过表达诱导过早的细胞分化,并导致分生组织终止表型。
这些发现确定了 IYO 作为拟南芥起始分化的必要和充分因素,并表明 IYO 的靶向核积累作为这个命运转变的转录开关的功能。