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，真核生物基因组，特别是植物基因组，通常主要由转座因子（TE）组成。这些元件复制并整合到不同的基因组位点，导致基因突变和显着的染色体改变。了解沉默的机制，这是启动，然后通过几代人保持，重要的是要掌握TE沉默和转座，形状基因组结构和影响基因调控之间的动态相互作用。然而，研究沉默启动是具有挑战性的，由于有限的新的发生以外的古老事件。这项研究建议利用玉米独有的两个天然存在的沉默子（杀手等位基因），这可以通过简单的杂交而不是使用转基因构建体来主动启动TE沉默。该研究旨在研究玉米表观遗传TE沉默的启动和后果，重点是响应发育线索的复杂调控机制。此外，该提案优先考虑学生参与，多样性支持和教育推广。通过促进初级本科院校（PUI）和研究密集型（R1）大学之间的合作，它旨在提高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。建立合作本科生研究经验（CURE）组件使更多的本科生从PUI从事真实的研究。此外，我们还为贫困学生量身定制了暑期研究奖学金计划，旨在克服他们缺乏研究机会和与学术界联系有限所带来的障碍，从而促进他们在STEM领域的成功。这项研究旨在深入了解植物发育过程中表观遗传机制和转座子沉默之间错综复杂的相互作用。具体目标包括：1）研究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，Acker衍生的小RNA利用RdDM沉默活性Ac转座子，通过这一途径提供了Ac沉默的第一个证据。该研究旨在研究Ack-小RNA对Ds的全基因组效应，以全面了解TE沉默过程中小RNA的靶向、启动和维持，并深入了解基因组进化过程中Ds的古老沉默事件。2)研究沉默机制的调控基于初步数据，即杀伤小RNA诱导的RdDM受发育阶段的严格调控。这种调节可能涉及不同沉默机制之间的交替，包括RdDM，组蛋白修饰和翻译抑制。通过研究相同的小RNA在不同组织中激活不同沉默途径的能力，这项研究提供了一个独特的机会来探索TE沉默响应发育线索的动态调节。该奖项反映了NSF的法定使命，并且通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。