BRC-BIO: Epigenetic Regulation of Transposable Elements in Maize

BRC-BIO：玉米转座元件的表观遗传调控

• 批准号: 2334573
• 负责人: Dafang Wang
• 金额: $ 45.24万
• 依托单位: Hofstra University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-06-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2334573&HistoricalAwards=false
• 关键词: BRC; BIO; Epigenetic; Regulation; Transposable

One surprising discovery of the genomics era is that eukaryotic genomes, particularly plant genomes, often consist largely of transposable elements (TEs). These elements replicate and integrate into various genomic sites, causing genetic mutations and significant chromosomal alterations. Understanding the mechanism of silencing, which is initiated and then maintained through generations, is important to grasp the dynamic interplay between TE silencing and transpositions that shapes genome structure and influences gene regulation. However, studying the silencing initiation is challenging due to the limited novel occurrence beyond ancient events. This study proposes utilizing two naturally occurring silencers (killer alleles) exclusive to maize, which can actively initiate TE silencing through simple crosses instead of using transgenic constructs. The research aims to investigate the initiation and consequences of epigenetic TE silencing in maize, with a focus on the sophisticated regulated mechanisms responding to developmental cues. Moreover, the proposal prioritizes student engagement, diversity support, and educational outreach. By fostering collaborations between Primarily Undergraduate Institutions (PUIs) and research-intensive (R1) universities, it seeks to enhance the PI's research productivity while addressing challenges faced by students in under-resourced environments. Incorporating a Collaborative Undergraduate Research Experience (CURE) component enables more undergraduate students from PUIs to engage in authentic research. Additionally, a summer research fellowship program tailored for underserved students is proposed, aiming to overcome barriers arising from their lack of research access and limited connections with the academic community, thereby promoting their success in STEM fields.This research aims to gain valuable insights into the intricate interplay between epigenetic mechanisms and transposon silencing during plant development. Specific goals include: 1) Studying the RNA-directed DNA methylation (RdDM) induced by maize killer alleles. Preliminary data indicate that Ackiller-derived small RNAs utilize RdDM to silence active Ac transposons, providing the first evidence of Ac silencing through this pathway. The study proposes to examine the genome-wide effects on Ds from the Ack-small RNAs to gain a comprehensive understanding of small RNA targeting, initiation, and maintenance during TE silencing, and obtain insights into the ancient silencing events on Ds during genome evolution. 2) Investigating the regulation of the silencing mechanisms based on the preliminary data that killer- small RNAs induced RdDM is tightly regulated by developmental stages. This regulation may involve alternating among different silencing mechanisms including RdDM, histone modification, and translation inhibition. By studying the ability of the same small RNAs to activate distinct silencing pathways in different tissues, this research provides a unique opportunity to explore the dynamic regulation of TE silencing in response to developmental cues.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

基因组学时代的一个令人惊讶的发现是，真核基因组，尤其是植物基因组，通常主要由可转移元素（TES）组成。这些元素复制并整合到各种基因组部位，引起基因突变和显着的染色体改变。了解沉默的机理，然后通过几代人开始并维持，这对于掌握了塑造基因组结构并影响基因调控的TE沉默与转置之间的动态相互作用很重要。但是，由于古代事件以外的新事件有限，研究沉默开始是具有挑战性的。这项研究建议利用玉米独有的两个天然存在的消音器（杀手等位基因），它们可以通过简单的十字而不是使用转基因构建体来主动启动沉默。该研究旨在研究玉米中表观遗传沉默的启动和后果，重点是对发展提示的复杂调节机制。此外，该提案优先考虑学生参与度，多样性支持和教育宣传。通过促进主要是本科机构（PUI）和研究密集型大学（R1）大学之间的合作，它试图提高PI的研究生产力，同时解决学生在资源不足的环境中面临的挑战。结合了协作的本科研究经验（CURE）组成部分，使更多的本科生从PUIS进行了真实的研究。此外，提出了针对服务不足的学生量身定制的夏季研究奖学金计划，旨在克服由于缺乏研究访问和与学术界的联系而引起的障碍，从而促进了他们在STEM领域的成功。这项研究旨在在工厂开发过程中对复杂的表观遗传机制和特种沉默之间的复杂互动的洞察力。具体目标包括：1）研究由玉米杀手等位基因诱导的RNA指导的DNA甲基化（RDDM）。初步数据表明，Ackiller衍生的小RNA利用RDDM沉默了活跃的AC转座子，这是通过该途径沉默的第一个证据。该研究建议检查ACK-SMALL RNA对DS的全基因组影响，以便在TE沉默过程中对小的RNA靶向，启动和维持的小小的理解，并在基因组演化过程中对DS上的古代沉默事件进行见解。 2）基于初步数据调查沉默机制，即杀手rNA诱导的RDDM受发育阶段严格调节。该调节可能涉及在包括RDDM，组蛋白修饰和翻译抑制在内的不同沉默机制之间交替。通过研究相同小型RNA在不同组织中激活不同的沉默途径的能力，这项研究为探索TE沉默的动态调节提供了一个独特的机会，以响应发育提示。该奖项反映了NSF的法定任务，并通过使用该基金会的智力功能和广泛的影响来评估Criteria审查Criteria。