Role of BEN domain proteins in chromatin organization and gene expression

基因表达的准确控制对细胞存活至关重要，并且显然依赖于染色质状态。染色质由DNA和组蛋白组成，组蛋白将DNA包裹成一个更紧密的结构。染色质结构可以通过多种方式进行修饰，以靶向特定的蛋白质结合，改变基因表达或启动DNA复制。该项目将确定一个特定的蛋白质如何改变真核生物基因组中的染色质组织和转录。这个跨学科的项目有很强的拓展成分，将吸引本科生参与研究，其中包括高分辨率显微镜和延时活细胞成像。本项目将包括本科女性和少数民族学生参与研究项目；为社区大学学生提供研究实习机会；支持一个活细胞成像的研讨会和研讨会。让年轻聪明的学生尽早参与研究将非常有益，并向他们灌输科学意识和潜力。蛋白质的功能通常可以通过域的存在来预测，域要么是不同的功能单元，要么是结构单元。这些结构域可以促进与特定蛋白质或核酸的结合。ben结构域是一种蛋白质结构域，存在于后生动物和病毒的多种蛋白质中。据预测，它介导蛋白质- dna和蛋白质-蛋白质相互作用，调节染色质组织和转录。BEN结构域蛋白作为一类参与基因调控的重要蛋白正迅速崛起。BANP/SMAR1、Mdg4、BEND等几种含ben蛋白具有染色质相关功能并调控基因表达。然而，含有ben结构域的基因家族如何调控染色质功能和转录的分子基础仍有待建立。该项目的目的是剖析含有四重ben结构域的蛋白BEND3的转录抑制的分子基础，并确定其在哺乳动物细胞中的生理作用。PIs实验室采用最先进的细胞生物学方法，包括延时成像、超分辨率结构照明成像，并将这些观察结果与生化方法相结合。该项目与美国国家科学基金会的使命相关，并将进一步理解一个基本的生物学问题：染色质组织如何决定转录调控。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Accurate control of gene expression is crucial for cell survival and is clearly dependent on the chromatin state. Chromatin consists of DNA plus histone proteins that wrap the DNA into a more compact structure. The chromatin structure can be modified in many ways to target specific protein binding, alter gene expression, or initiate DNA replication. The project will determine how a particular protein alters chromatin organization and transcription within the eukaryotic genome. This interdisciplinary project has a strong outreach component and will engage undergraduate students in research, which will include high-resolution microscopy as well as time-lapse live cell imaging. This project will include undergraduate women and minority students in the research project; provide opportunities for community college students via research internships; and support a workshop and symposium on live cell imaging. Exposing young and bright students to research early on will be highly beneficial and instill in them a sense of scientific awareness and potential. The function of a protein can often be predicted by the presence of domains that are either distinct functional or structural units. These domains can promote binding to specific proteins or nucleic acids. The BEN-domain is a protein domain that is present in diverse proteins in metazoans as well as in viruses. It is predicted to mediate protein-DNA and protein-protein interactions to regulate chromatin organization and transcription. BEN domain-containing proteins are emerging rapidly as an important class of proteins involved in gene regulation. Several BEN-containing proteins including BANP/SMAR1, Mdg4, BEND have chromatin-related functions and regulate gene expression. However, the molecular basis of how the BEN-domain containing gene family regulates chromatin function and transcription remains to be established. The objective of the project is to dissect the molecular basis of transcription repression by the quadruple BEN-domain containing protein BEND3 and determine its physiological role in mammalian cells. The PIs laboratory utilizes state-of the art cell biological approaches including time-lapse imaging, super-resolution structural illumination imaging and combines these observations with biochemical approaches. This project is relevant to the NSF mission and will further the understanding of a basic biology question: how chromatin organization dictates transcriptional regulation.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.