Analysis of divergent transcripts in estrogen-dependent signaling.

雌激素依赖性信号传导中不同转录本的分析。

基本信息

批准号：
10629619
负责人：
Shrikanth Gadad
金额：
$ 16万
依托单位：
TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER AT EL PASO
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-10 至 2027-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10629619
关键词：
Address Affect Androgens Binding Biochemical Biochemistry Biological Assay Breast Cardiovascular Diseases Cell Fractionation Cell Nucleus Cell physiology Cells Cellular biology Cessation of life Chromatin Chromatin Loop Code Collaborations Communication Communities Complex County DNA Polymerase II Data Dimerization Disease Elements Endocrine Enhancers Enzymes Epigenetic Process Estrogen Receptor alpha Estrogen receptor positive Estrogens Federal Government Fibroid Tumor Functional disorder Gene Combinations Gene Expression Gene Expression Profiling Genes Genetic Transcription Genomic Segment Genomic approach Genomics Goals Growth Hispanic-serving Institution Histones Hormones Ligands MCF7 cell Molecular Molecular Mechanisms of Action Outcome Pathway interactions Pattern Play Positioning Attribute Proliferating Property Proteins Proteomics RNA Regulator Genes Research Role Signal Transduction Site Texas Tissues Transcript Untranslated RNA cell growth chromatin remodeling endometriosis epigenomics global run on sequencing insight malignant breast neoplasm novel programs promoter receptor recruit response spatiotemporal tool transcriptome sequencing

项目摘要

Project Summary The endocrine hormone estrogen (E2) actions by binding to its estrogen-receptor alpha (ERα), stimulates a robust mitogenic response in ER+ cells. In this regard, signal-regulated divergent transcription and its products have emerged as an important class of molecules that regulate various endocrine pathways such as estrogen and androgen signaling. Recent studies suggest that divergent transcripts are cell- and tissue-specifically expressed, and the E2-regulated divergent transcription is critical to eliciting full E2-driven gene expression. E2 signaling triggers a highly coordinated transcriptional program, leading to a robust mitogenic response that drives different cellular activities. Understanding the molecular mechanisms through which divergent transcription or transcripts regulate E2-responsive, ERα-dependent transcription will increase our understanding of the diseases caused by aberrant E2-signaling. Deciphering the molecular mechanisms of action of divergent transcripts in ER+ cells will be very important. In the preliminary study involving cellular and genomic approaches, E2- regulated divergent RNAs were identified and annotated. In addition, the initial characterization of a novel E2- regulated divergent transcript suggests that it controls E2-driven cellular processes and gene expression. In the current proposal, the molecular mechanisms by which divergent transcripts regulate E2-dependent signaling will be determined. The overarching hypothesis is that specific biochemical and structural properties of divergent transcripts underlie their ability to control critical E2-dependent pathways. A complementary set of biochemical, molecular, cell-based, proteomic, and genomic assays will be used to study the molecular mechanisms by which divergent transcript regulates E2-dependent transcription and growth of ER+ cells: specifically (1) Aim 1 will determine the molecular mechanisms of action of E2-regulated divergent transcript, in E2-dependent signaling, and (2) Aim 2 will identify the mechanism by which divergent transcripts control the assembly of E2-dependent gene regulatory complex. Successful completion of these aims will yield a new understanding of how divergent transcripts control key E2-dependent cellular pathways.

项目摘要通过与其雌激素受体α（ERα）结合，内分泌激素雌激素（E2）作用刺激 ER+细胞中强大的有丝分裂反应。在这方面，信号调节的发散转录及其产物已成为一种重要的分子，这些分子调节各种内分泌途径，例如雌激素和雄激素信号传导。最近的研究表明，不同的转录本特定于细胞和组织。表达，E2调节的发散转录对于引发全E2驱动的基因表达至关重要。 E2 信号传导触发高度协调的转录程序，导致良好的有丝分裂反应驱动不同的细胞活性。了解分子机制通过哪些分子转录或转录本调节E2响应性，依赖ERα的转录将增加我们对疾病的理解由异常的E2信号引起。解解发散转录本作用的分子机制 ER+细胞将非常重要。在初步研究中，涉及细胞和基因组方法，E2- 鉴定并注释受调节的发散RNA。另外，新型E2-的初始表征调节的发散转录本表明它控制了E2驱动的细胞过程和基因表达。在当前的建议，分子机制，通过该提议调节E2依赖性信号的分子机制将可以确定。总体假设是发散的特定生化和结构特性成绩单是控制关键E2依赖途径的能力。一组完整的生化，分子，基于细胞的，蛋白质组学和基因组测定将用于研究分子机制发散转录本调节E2依赖性转录和ER+细胞的生长：特别是（1）AIM 1 Will 在E2依赖性信号传导中确定E2调节的发散转录本的作用分子机制，（2）AIM 2将确定发散转录本控制E2依赖性组装的机制基因调节复合物。这些目标的成功完成将对如何发散产生新的了解转录本控制钥匙E2依赖性细胞途径。