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.

项目概要内分泌激素雌激素 (E2) 通过与其雌激素受体 α (ERα) 结合而发挥作用，刺激 ER+细胞中强烈的有丝分裂反应在这方面，信号调节的分歧转录及其产物。已成为调节雌激素等多种内分泌途径的一类重要分子最近的研究表明，不同的转录本具有细胞和组织特异性。表达，并且 E2 调节的发散转录对于引发 E2 驱动的基因完全表达至关重要。信号传导触发高度协调的转录程序，导致强大的有丝分裂反应，从而驱动了解不同转录或不同细胞活动的分子机制。转录本调节 E2 响应、ERα 依赖性转录将增加我们对疾病的了解破译不同转录本的分子作用机制。在涉及细胞和基因组方法的初步研究中，E2- 细胞将非常重要。此外，还鉴定并注释了新型 E2-的初步表征。受调节的发散转录本表明它控制 E2 驱动的细胞过程和基因表达。目前的建议是，不同转录本调节 E2 依赖性信号传导的分子机制将总体假设是不同的特定生化和结构特性。转录本是其控制关键 E2 依赖性途径的能力的基础。分子、细胞、蛋白质组和基因组检测将用于研究分子机制发散转录物调节 ER+ 细胞的 E2 依赖性转录和生长：特别是 (1) 目标 1 将确定 E2 调节的不同转录物在 E2 依赖性信号传导中的分子作用机制， (2) 目标 2 将确定不同转录本控制 E2 依赖性组装的机制基因调控复合体的成功完成将产生对差异的新认识。转录本控制关键的 E2 依赖性细胞通路。