Vernalization a cold-induced regulatory network establishing cellular memory

描述(由申请人提供)：在多细胞生物体的发育过程中，细胞分化总是涉及基因表达模式的变化。在许多发育项目中，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，在没有引起变化的原始信号的情况下，这种基因表达变化在随后的细胞分裂中保持稳定。在动物中，表观遗传开关经常“锁定”发育命运，就像在胚胎发育期间建立身体计划时发生的那样。在许多植物中，春化引起的类似的表观遗传开关被用来控制生殖能力。春化是植物通过测量暴露在冬季寒冷中的持续时间，并在感知到足够的寒冷持续时间后，获得来年春天开花的能力的过程。通过对FLC染色质的组蛋白进行一系列的修饰，开花抑制基因FLC的表观遗传沉默导致了对花的抗性。我们将结合对自然变异、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，以确定春化网络的构成要素。我们将定义伴随着能力获得的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。我们计划研究的调控网络与动物的身体规划和器官形成有相似之处。此外，我们正在研究的表观遗传开关在减数分裂过程中被重置，这也是哺乳动物基因组印记的一个特征。对表观遗传过程的不正确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体的表观遗传调控的一般理解最终应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.