Role of BEN domain proteins in chromatin organization and gene expression

BEN 结构域蛋白在染色质组织和基因表达中的作用

• 批准号: 1818286
• 负责人: Supriya Prasanth
• 金额: $ 71.4万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1818286&HistoricalAwards=false
• 关键词: Role; BEN; domain; proteins; chromatin

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.

基因表达的准确控制对于细胞生存至关重要，并且显然取决于染色质状态。染色质由 DNA 和组蛋白组成，组蛋白将 DNA 包裹成更紧凑的结构。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。该项目将确定特定蛋白质如何改变真核基因组内的染色质组织和转录。 这个跨学科项目具有强大的外展成分，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。该项目将包括本科女性和少数民族学生的研究项目；通过研究实习为社区学院学生提供机会；并支持活细胞成像研讨会和研讨会。让年轻聪明的学生尽早接触研究将非常有益，并灌输他们的科学意识和潜力。蛋白质的功能通常可以通过作为不同功能或结构单元的域的存在来预测。 这些结构域可以促进与特定蛋白质或核酸的结合。 BEN 结构域是存在于后生动物和病毒的多种蛋白质中的蛋白质结构域。预计它会介导蛋白质-DNA 和蛋白质-蛋白质相互作用，从而调节染色质组织和转录。含有 BEN 结构域的蛋白质正在迅速成为参与基因调控的一类重要蛋白质。包括 BANP/SMAR1、Mdg4、BEND 在内的几种含有 BEN 的蛋白具有染色质相关功能并调节基因表达。然而，含 BEN 结构域的基因家族如何调节染色质功能和转录的分子基础仍有待确定。该项目的目标是剖析含有四重 BEN 结构域的蛋白质 BEND3 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。 PI 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 NSF 的使命相关，将进一步加深对基本生物学问题的理解：染色质组织如何决定转录调控。该奖项反映了 NSF 的法定使命，并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。

项目成果

DNA Damage-Induced, S-Phase Specific Phosphorylation of Orc6 is Critical for the Maintenance of Genome Stability

• DOI: 10.1080/10985549.2023.2196204
• 发表时间: 2023-04
• 期刊: Molecular and Cellular Biology
• 影响因子: 5.3
• 作者: Yo-Chuen Lin;Dazhen Liu;Arindam Chakraborty;V. Macias;Eileen Brister;Jay Sonalkar;Linyuan Shen;Jaba Mitra;T. Ha;A. Kajdacsy-Balla;K. Prasanth;S. Prasanth

LncRNA-mediated regulation of SOX9 expression in basal subtype breast cancer cells

• DOI: 10.1261/rna.073254.119
• 发表时间: 2020-02-01
• 期刊: RNA
• 影响因子: 4.5
• 作者: Tariq, Aamira;Hao, Qinyu;Prasanth, Kannanganattu V.
• 通讯作者: Prasanth, Kannanganattu V.

A natural antisense lncRNA controls breast cancer progression by promoting tumor suppressor gene mRNA stability.

• DOI: 10.1371/journal.pgen.1007802
• 发表时间: 2018-11
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Jadaliha M;Gholamalamdari O;Tang W;Zhang Y;Petracovici A;Hao Q;Tariq A;Kim TG;Holton SE;Singh DK;Li XL;Freier SM;Ambs S;Bhargava R;Lal A;Prasanth SG;Ma J;Prasanth KV
• 通讯作者: Prasanth KV

MIR100 host gene-encoded lncRNAs regulate cell cycle by modulating the interaction between HuR and its target mRNAs.

• DOI: 10.1093/nar/gky696
• 发表时间: 2018-11-02
• 期刊: Nucleic acids research
• 影响因子: 14.9
• 作者: Sun Q;Tripathi V;Yoon JH;Singh DK;Hao Q;Min KW;Davila S;Zealy RW;Li XL;Polycarpou-Schwarz M;Lehrmann E;Zhang Y;Becker KG;Freier SM;Zhu Y;Diederichs S;Prasanth SG;Lal A;Gorospe M;Prasanth KV
• 通讯作者: Prasanth KV

The E3 ligase RFWD3 stabilizes ORC in a p53-dependent manner

E3 连接酶 RFWD3 以 p53 依赖性方式稳定 ORC

• DOI: 10.1080/15384101.2020.1829823
• 发表时间: 2020
• 期刊: Cell Cycle
• 影响因子: 4.3
• 作者: Hsu, Rosaline Y.C.;Giri, Sumanprava;Wang, Yating;Lin, Yo-Chuen;Liu, Dazhen;Wopat, Susan;Chakraborty, Arindam;Prasanth, Kannanganattu V.;Prasanth, Supriya G.
• 通讯作者: Prasanth, Supriya G.