Molecular Mechanism of Photoperiodic Time Measurement

描述(申请人提供)：不能对季节变化作出适当反应的生物体将面临与生存和繁殖有关的严重后果。对于人类来说，光照的季节性变化会导致季节性情感障碍(SAD)，这是抑郁症的一种反复发作的亚型。虽然SAD的分子机制仍不清楚，但众所周知，光周期机制在许多SAD病例中发挥着重要作用。许多生物，包括人类，已经进化出感知日长变化(光周期)的机制，并将季节性变化信息整合到它们的发育中。我们研究计划的长期目标是阐明生物测量日长变化的分子机制，并相应地调整它们的行为和发育。虽然光周期作用的分子机制在许多生物中还没有得到很好的描述，但模式植物拟南芥的研究进展增加了我们对光周期时间测量的分子理解，并影响了其他动植物物种的研究。在拟南芥中，核心的时间测量机制是花激活因子Constans(CO)基因的昼夜调控转录和光调控的CO蛋白的稳定性和活性。在这项提案中，将通过生化、遗传和基因组方法对这一核心机制进行进一步的表征。在目标1中，将描述新发现的CO转录调控因子。这些发现将进一步阐明生物钟如何通过协调不同类别的转录因子在调节季节性反应中发挥作用。在目标2中，将研究一氧化碳转录调控的依赖于时间的染色质修饰--一个新的理解机制层--。我们以前的研究结果表明，FKF1蓝光感受器参与了CO蛋白的翻译后调节。目的3研究FKF1结合蛋白在CO蛋白稳定性调节中的分子功能。有了这三个目标，我们将分析植物通过生物钟监测每日和季节差异的机制。这些发现将影响植物研究，以及我们对哺乳动物和其他系统中的光周期和生物钟的更广泛理解。拟南芥中存在的转录和翻译后机制的类型在所有真核生物中可能是保守的，因此这些发现将有助于我们理解基本的转录调控。这些发现也有可能为SAD涉及的机制提供线索。最后，阐明光周期开花机制对于理解直接适用于提高作物产量的主要植物繁殖机制非常重要，作物产量是人类健康的重要贡献者，特别是在发展中国家。

DESCRIPTION (provided by applicant): Organisms that fail to respond appropriately to seasonal change will face severe consequences related to survival and reproduction. For humans, seasonal variation in the amount of light causes Seasonal Affective Disorder (SAD), a recurrent subtype of depression. Although the molecular mechanisms underlying SAD remain elusive, it is known that photoperiodic mechanisms play a significant role in many cases of SAD. Many organisms, including humans, have evolved mechanisms to sense changes in day length (=photoperiod) and integrate seasonal change information into their development. The long-term goal of our research program is to elucidate the molecular mechanisms by which organisms measure changes in day length and adjust their behaviors and development accordingly. Although the molecular mechanisms of photoperiodism have not yet been well described in many organisms, recent advances in the study of the model plant Arabidopsis have increased our molecular understanding of photoperiodic time measurement and have influenced the study of other plant and animal species. In Arabidopsis, the core time-measurement mechanism is circadian-regulated transcription of the floral activator CONSTANS (CO) gene and light-regulated CO protein stability and activity. In this proposal, further characterization o this core mechanism will be done through biochemical, genetic, and genomic approaches. In Aim 1, newly identified transcriptional regulators of CO will be characterized. The findings will elucidate further how the circadian clock plays a role in regulating seasonal response by orchestrating different classes of transcription factors. In Aim 2, time-dependent chromatin modification of CO transcriptional regulation - a new mechanistic layer of understanding - will be studied. Our previous results indicated the involvement of the FKF1 blue-light photoreceptor in posttranslational regulation of CO protein. In Aim 3, the molecular function of FKF1-associating proteins on CO protein stability regulation will be examined. With these three Aims, the mechanisms by which plants monitor daily and seasonal differences through the circadian clock will be analyzed. The findings will impact plant research and our broader understanding of photoperiodism and circadian clocks in mammals and other systems. The types of transcriptional and posttranslational mechanisms present in Arabidopsis are likely conserved among all eukaryotes, thus these findings will contribute to our understanding of fundamental transcriptional regulation. These findings also have the potential to provide clues to the mechanisms involved in SAD. Finally, elucidating the photoperiodic flowering mechanism is important for understanding a major plant reproduction mechanism that is directly applicable to improvements in crop yield, an important contributor to human health especially in developing countries.