Vernalization a cold-induced regulatory network establishing cellular memory

描述（由申请人提供）：在多细胞生物的发育过程中，细胞分化总是涉及基因表达模式的变化。在许多发育过程中，基因表达模式的某些关键变化本质上是表观遗传的；也就是说，这种基因表达的变化在缺乏诱导变化的原始信号的情况下，通过随后的细胞分裂保持稳定。在动物中，表观遗传开关经常“锁定”发育命运，例如发生在胚胎发生期间身体计划的建立中。在许多植物中，由春化产生的类似的表观遗传开关被用来控制生殖能力。春化是植物测量暴露于冬季寒冷的持续时间，并在感知到足够的寒冷持续时间后，获得下一个春天开花的能力的过程。开花抑制因子开花位点C （FLC）通过对FLC染色质组蛋白的一系列修饰而被表观遗传沉默，从而获得开花能力。我们将结合自然变异、突变筛选、蛋白质相互作用筛选和全基因组基因表达模式的研究来确定春化网络的构成要素。我们将定义伴随能力获得的FLC染色质的具体变化。然后，我们将讨论春化过程中涉及的基因产物的作用和相互作用。我们工作的一个长期目标是了解基因调控网络是如何运作的。我们拟研究的调控网络与动物身体规划和器官形成的调控网络有相似之处。此外，我们正在研究的表观遗传开关在减数分裂期间被重置，这也是哺乳动物基因组印记的一个特征。表观遗传过程的不当调控可能是异常发育事件和某些疾病状态（如癌症）的基础。对一系列多细胞生物的表观遗传调控的一般理解应该最终有助于制定治疗疾病状态的策略。

DESCRIPTION (provided by applicant): Cellular differentiation-in the development of multicellular organisms invariably involves changes-in patterns of gene expression. In many developmental programs, certain key changes in patterns of gene expression are epigenetic in nature; that is, such changes in gene expression remain stable through subsequent cell divisions in the absence of the original signal that induced the changes. In animals, epigenetic switches often "lock in" developmental fates such as occurs in establishment of the body plan during embryogenesis. In many plants, a comparable epigenetic switch resulting from vernalization is used to govern reproductive competence. Vernalization is the process by which plants measure the duration of exposure to winter's cold and, after perceiving a sufficient duration of cold, acquire competence to flower the following spring. Competence to flower results from the epigenetic silencing of a flowering repressor, FLOWERING LOCUS C (FLC), via a series of modifications to histones of FLC chromatin. We will combine studies of natural variation, mutant screens, protein interaction screens, and genome-wide gene expression patterns to identify constitutive elements of the vernalization network. We will define the specific changes in FLC chromatin that accompany the acquisition of competence. We will then address the roles and interaction of the genes product involved in vernalization. A long-term goal of our work is to understand how genetic regulatory networks operate. The regulatory network that we propose to study has similarities to those involved in body plan and organ formation in animals. Moreover, the epigenetic switch that we are studying is reset during meiosis which is also a feature of genomic imprinting in mammals. Improper regulation of epigenetic processes can underlie abnormal developmental events and some disease states such as cancer. A general understanding of epigenetic regulation in a range of multi-cellular organisms should ultimately contribute to the development of strategies to treat disease states.