Tan-Wong Sue Mei, Wijayatilake Hashanthi D, Proudfoot Nick J
Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, United Kingdom.
Genes Dev. 2009 Nov 15;23(22):2610-24. doi: 10.1101/gad.1823209.
Inducible genes in yeast retain a "memory" of recent transcriptional activity during periods of short-term repression, allowing them to be reactivated faster when reinduced. This confers a rapid and versatile gene expression response to the environment. We demonstrate that this memory mechanism is associated with gene loop interactions between the promoter and 3' end of the responsive genes HXK1 and GAL1FMP27. The maintenance of these memory gene loops (MGLs) during intervening periods of transcriptional repression is required for faster RNA polymerase II (Pol II) recruitment to the genes upon reinduction, thereby facilitating faster mRNA accumulation. Notably, a sua7-1 mutant or the endogenous INO1 gene that lacks this MGL does not display such faster reinduction. Furthermore, these MGLs interact with the nuclear pore complex through association with myosin-like protein 1 (Mlp1). An mlp1Delta strain does not maintain MGLs, and concomitantly loses transcriptional memory. We predict that gene loop conformations enhance gene expression by facilitating rapid transcriptional response to changing environmental conditions.
酵母中的可诱导基因在短期抑制期间保留了近期转录活性的“记忆”,使其在再次诱导时能够更快地重新激活。这赋予了对环境快速且多样的基因表达反应。我们证明这种记忆机制与响应基因HXK1和GAL1FMP27的启动子和3'端之间的基因环相互作用有关。在转录抑制的中间阶段维持这些记忆基因环(MGL)是重新诱导时RNA聚合酶II(Pol II)更快募集到基因上所必需的,从而促进更快的mRNA积累。值得注意的是,缺乏这种MGL的sua7-1突变体或内源性INO1基因不会表现出如此快速的重新诱导。此外,这些MGL通过与肌球蛋白样蛋白1(Mlp1)结合而与核孔复合体相互作用。mlp1Delta菌株不能维持MGL,并且随之失去转录记忆。我们预测基因环构象通过促进对不断变化的环境条件的快速转录反应来增强基因表达。