Mechanisms of chromatin and transcriptional regulation

染色质和转录调控机制

• 批准号: 10552419
• 负责人: Brian D Strahl
• 金额: $ 58.65万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10552419
• 关键词: Address; Award; Binding; Biology; Chromatin; Complex; DNA Packaging; Defect; Enzymes; Event; Genetic Transcription; Genome; Goals; Histones; Knowledge; Malignant Neoplasms; Modification; Molecular; Molecular Chaperones; Nucleosomes; Post-Translational Protein Processing; Proteins; Reader; Regulation; Research Design; Therapeutic Intervention; Transcriptional Regulation; Variant; human disease; new therapeutic target

Our long-term goal has been to reveal the molecular mechanisms of histone-modifying enzymes, histone chaperones and other transcriptional regulators that control genome function. Many of the proteins and their modifications we study are dysregulated in human disease, including cancer. Despite considerable progress by our lab and others, crucial knowledge gaps remain in our fundamental understanding of chromatin regulation. With the renewal of this MIRA award, we will continue our studies into the function of chromatin regulators and address three of the foremost fundamental questions in chromatin biology: 1) How do histone-modifying enzymes and chaperones contribute to chromatin organization and gene transcription? 2) How do more recently discovered histone PTMs and reader domains contribute to gene transcription? 3) What are the rules by which histone readers engage nucleosomes and how do these binding events regulate downstream events in chromatin? For each question, we highlight several examples of the types of studies we are pursuing and describe how they will advance the field.

我们的长期目标是揭示组蛋白修饰的分子机制

项目成果

Catalysis-dependent and redundant roles of Dma1 and Dma2 in maintenance of genome stability in Saccharomyces cerevisiae.

• DOI: 10.1016/j.jbc.2021.100721
• 发表时间: 2021-01
• 期刊: The Journal of biological chemistry
• 作者: Yoblinski AR;Chung S;Robinson SB;Forester KE;Strahl BD;Dronamraju R
• 通讯作者: Dronamraju R

Mechanically transduced immunosorbent assay to measure protein-protein interactions.

• DOI: 10.7554/elife.67525
• 发表时间: 2021-09-28
• 期刊: eLife
• 影响因子: 7.7
• 作者: Petell CJ;Randene K;Pappas M;Sandoval D;Strahl BD;Harrison JS;Steimel JP
• 通讯作者: Steimel JP

Spt6 Association with RNA Polymerase II Directs mRNA Turnover During Transcription.

• DOI: 10.1016/j.molcel.2018.05.020
• 发表时间: 2018-06-21
• 期刊: Molecular cell
• 影响因子: 16
• 作者: Dronamraju R;Hepperla AJ;Shibata Y;Adams AT;Magnuson T;Davis IJ;Strahl BD
• 通讯作者: Strahl BD

Molecular mechanism of the MORC4 ATPase activation.

• DOI: 10.1038/s41467-020-19278-8
• 发表时间: 2020-10-29
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Tencer AH;Cox KL;Wright GM;Zhang Y;Petell CJ;Klein BJ;Strahl BD;Black JC;Poirier MG;Kutateladze TG
• 通讯作者: Kutateladze TG

The ZZ domain of HERC2 is a receptor of arginylated substrates.

• DOI: 10.1038/s41598-022-10119-w
• 发表时间: 2022-04-11
• 期刊: SCIENTIFIC REPORTS
• 影响因子: 4.6
• 作者: Tencer, Adam H.;Liu, Jiuyang;Zhu, Jing;Burkholder, Nathaniel T.;Zhang, Yi;Wu, Wenwen;Strahl, Brian D.;Ohta, Tomohiko;Kutateladze, Tatiana G.
• 通讯作者: Kutateladze, Tatiana G.