Novel Coregulators of Estrogen Receptor in Enhancer-regulated Transcription

增强子调节转录中雌激素受体的新型共调节因子

基本信息

批准号：
10798780
负责人：
Zhijie Jason Liu
金额：
$ 3.27万
依托单位：
UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10798780
关键词：
Address Antiestrogen Therapy Binding Biological Biotin Breast Cancer cell line Cell Fate Control Cell Line Cell Separation Cells ChIP-seq Chromatin DNA DNA Binding Data Defect Development Disease Disease Resistance Distal EP300 gene Enhancers Epigenetic Process Equipment Estradiol Estrogen Receptor alpha Estrogen Receptors Estrogens Flow Cytometry Foundations Functional disorder Funding Future Gene Expression Gene Expression Profile Genetic Transcription Genomics Goals Grant Hormones Image Individual Knock-out Knowledge Mammary gland Mediating Mediator Methodology Modeling Molecular Names Nuclear Receptors Organ Pathway interactions Phenotype Play Proteins Proteomics Regulation Regulatory Element Reporting Resistance Role Running Tamoxifen Technology Testing Untranslated RNA Xenograft procedure cell growth cofactor combinatorial conditional knockout global run on sequencing hormone resistance improved in vivo knock-down mammary gland development mouse model novel overexpression parent grant programs receptor function recruit targeted treatment transcription factor user-friendly

项目摘要

SUMMARY/ABSTRACT Novel Coregulators of Estrogen Receptor in Enhancer-regulated Transcription Estrogen (E2 or 17β-estradiol) and its nuclear receptor ERα play a critical role in the normal development and disease conditions of multiple organs, including the mammary glands, by binding mostly to distal enhancers. Increasing evidence suggests that functional dysregulation of ERα-bound enhancers can profoundly alter normal transcriptional programs, resulting in developmental defects, diseases, and hormone resistance. However, the molecular mechanisms underlying enhancer function/dysfunction are largely unknown. One of the main objectives of the parent grant, R01GM137009, is to understand how the cooperative interactions between YAP/TEAD and ERα control the context-specific function of ERα-bound enhancers in vivo through enhancer reprogramming. Specifically relevant to this supplement application, we aim to determine the functional attributes of YAP/TEAD in enhancer reprogramming during mammary gland development. To achieve this goal, we plan to dissect mammary glands from mouse models (YAP knockout and overexpression models) and isolate single cells for cell sorting or cellular phenotype analysis through flow cytometry. We are requesting equipment funding to purchase a single-cell dissociator combined with a user-friendly flow cytometer that will allow us to perform phenotype analysis of the mammary glands. This equipment is critical for my lab to complete this parental R01 project.

摘要/摘要增强子注射转录中雌激素受体的新型核心观念剂雌激素（E2或17β-雌二醇）及其核受体ERα在正常发育中起关键作用以及多个器官的疾病状况，不乳腺，主要通过远端结合增强子。深刻改变正常的转录程序，导致发育缺陷，疾病和激素电阻。但是，增强子功能/功能障碍的分子机制未知 YAP/TEAD与ERα之间的相互作用控制控制控制控制。通过增强器重编程，与补充应用有关，我们旨在确定您在乳腺发育过程中，增强子重生中的YAP/TEAD的功能属性实现此目标，我们计划从鼠标模型中挖掘乳腺模型）和通过流动率进行的细胞分类或细胞表型分析要求购买设备资金以购买单细胞解离器与用户友好的流程相结合 cyot仪将使我们能够对乳腺进行分析。让我的实验室完成这个父母R01项目。