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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.

总结/摘要增强子调控的雌激素受体转录中的新型辅助调节因子雌激素（E2或17 β-雌二醇）及其核受体ER α在正常发育过程中起重要作用和疾病状况的多个器官，包括乳腺，通过结合主要是远端增强剂。越来越多的证据表明，ER α结合增强子的功能失调可以深刻地改变正常的转录程序，导致发育缺陷，疾病和激素阻力然而，增强子功能/功能障碍的分子机制在很大程度上是未知母公司赠款R01GM137009的主要目标之一是了解合作社如何雅普/TEAD和ER α之间的相互作用控制了ER α结合增强子在体内的特异性功能通过增强子重编程。特别是与本补充申请相关的，我们旨在确定雅普/TEAD在乳腺发育过程中增强子重编程中的功能属性。到为了实现这一目标，我们计划从小鼠模型（雅普敲除和过表达）中解剖乳腺模型）并分离单细胞用于细胞分选或通过流式细胞术进行细胞表型分析。我们要求设备资金购买单细胞解离器结合用户友好的流程这将使我们能够进行乳腺的表型分析。这些设备至关重要来完成这个亲代R01项目