Szent-Gyorgyi C
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA.
Mol Cell Biol. 1995 Dec;15(12):6754-69. doi: 10.1128/MCB.15.12.6754.
Although key genetic regulators of early meiotic transcription in Saccharomyces cerevisiae have been well characterized, the activation of meiotic genes is still poorly understood in terms of cis-acting DNA elements and their associated factors. I report here that induction of HSP82 is regulated by the early meiotic IME1-IME2 transcriptional cascade. Vegetative repression and meiotic induction depend on interactions of the promoter-proximal heat shock element (HSE) with a nearby bipartite repression element, composed of the ubiquitous early meiotic motif, URS1 (upstream repression sequence 1), and a novel ancillary repression element. The ancillary repression element is required for efficient vegetative repression, is spatially separable from URS1, and continues to facilitate repression during sporulation. In contrast, URS1 also functions as a vegetative repression element but is converted early in meiosis into an HSE-dependent activation element. An early step in this transformation may be the antagonism of URS1-mediated repression by IME1. The HSE also nonspecifically supports a second major mode of meiotic activation that does not require URS1 but does require expression of IME2 and concurrent starvation. Interestingly, increased rather than decreased URS1-mediated vegetative transcription can be artificially achieved by introducing rare point mutations into URS1 or by deleting the UME6 gene. These lesions offer insight into mechanisms of URS-dependent repression and activation. Experiments suggest that URS1-bound factors functionally modulate heat shock factor during vegetative transcription and early meiotic induction but not during heat shock. The loss of repression and activation observed when the IME2 activation element, T4C, is substituted for the HSE suggests specific requirements for URS1-upstream activation sequence interactions.
尽管酿酒酵母早期减数分裂转录的关键遗传调节因子已得到充分表征，但就顺式作用DNA元件及其相关因子而言，减数分裂基因的激活仍知之甚少。我在此报告，HSP82的诱导受早期减数分裂IME1-IME2转录级联调节。营养生长抑制和减数分裂诱导取决于启动子近端热休克元件（HSE）与附近一个二分抑制元件的相互作用，该二分抑制元件由普遍存在的早期减数分裂基序URS1（上游抑制序列1）和一个新的辅助抑制元件组成。辅助抑制元件是有效营养生长抑制所必需的，在空间上可与URS1分离，并在孢子形成过程中继续促进抑制作用。相比之下，URS1也作为营养生长抑制元件发挥作用，但在减数分裂早期转变为依赖HSE的激活元件。这种转变的早期步骤可能是IME1对URS1介导的抑制的拮抗作用。HSE还非特异性地支持减数分裂激活的第二种主要模式，该模式不需要URS1，但需要IME2的表达和同时的饥饿状态。有趣的是，通过在URS1中引入罕见的点突变或删除UME6基因，可以人为地实现URS1介导的营养生长转录增加而非减少。这些损伤有助于深入了解URS依赖性抑制和激活机制。实验表明，在营养生长转录和早期减数分裂诱导过程中，与URS1结合的因子在功能上调节热休克因子，但在热休克过程中则不然。当用IME2激活元件T4C替代HSE时观察到的抑制和激活的丧失表明对URS1-上游激活序列相互作用有特定要求。
