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Underlying chromatin architecture defines functionality for CFTR expression

底层染色质架构定义了 CFTR 表达的功能

基本信息

批准号：
10477362
负责人：
Martin John Walsh
金额：
$ 42.38万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10477362
关键词：
ATAC-seq Address Affinity Affinity Chromatography Alleles Architecture Binding Proteins Biochemistry Biological Biological Sciences Biology CCCTC-binding factor CHD4 gene CRISPR/Cas technology Cells ChIP-seq Chromatin Clustered Regularly Interspaced Short Palindromic Repeats Code Complement Complex Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator DNA Deacetylase Dependence Development Disease Outcome Elements Engineering Enhancers Environment Epigenetic Process Epithelial Cells Fibroblasts Funding Gene Expression Genes Genetic Genetic Polymorphism Genetic Transcription Genome engineering Genomic Segment Genomics Goals Guide RNA Histone Deacetylase Inhibitor Histones Human Human Genome Intestines Introns Knowledge Learning Link Lung Maps Mass Spectrum Analysis Measures Mediating Methods Molecular Mutation Nucleosomes Pancreatic duct Pancreatitis Pathway interactions Phenotype Positioning Attribute Post-Translational Protein Processing Predisposition Prenatal Diagnosis Procedures Process Protein Binding Domain Proteins Proteome Proteomics RNA Regulation Regulator Genes Repression Research Project Grants Resolution Role Shapes Site Spectrophotometry Technology Therapeutic Therapeutic Intervention Transcript United States National Institutes of Health bronchial epithelium cell type chromatin remodeling epigenome expectation experience functional genomics gene product gene repression genome editing genomic locus helicase histone modification human disease insight knock-down mouse model new therapeutic target novel novel strategies outcome prediction penis foreskin public health relevance targeted treatment transcription termination transcriptome sequencing

项目摘要

PROJECT SUMMARY: The overall goal of this application is to elucidate the biological impact of chromatin remodeling for the regulation of the cystic fibrosis transmembrane conductance regulator gene (CFTR) locus. In turn, a novel understanding of chromatin remodeling processes linked with gene transcription may enable novel approaches to targeted therapy for enriching weak (or poor) CFTR expression that appear consistent with specific mutations in CFTR. This new knowledge coincides with the overall expectation to understand the complex relationship of CFTR expression to cystic fibrosis (CF). CF remains a prominent genetic defect where significant progress has been made in prenatal diagnosis and treatment. While many coding mutations in the CFTR gene have been identified and casually linked to CF as a human disease, various non-genic polymorphisms remain an unknown contributor the spectrum of disease outcomes link to the CFTR gene and its expression. We, and others, have provided new insight about the chromatin architecture behind the CFTR locus that gives rise to the selective epithelial cell-type and development control of CFTR transcription. In the previous funding cycle we have identified and confirmed the role of the chromo-helicase DNA binding domain protein 6 (CHD6) lies at the core of the topologically well-organized CFTR gene in native chromatin. This has provided new insight as to the factors that govern how CFTR is arranged in the chromatin context in cultured and primary cells. Together, through the aims proposed we expect to provide the fundamental framework to determine how CFTR expression is guiding under a native chromatin context. We envision that these studies will deepen our understanding of the means chromatin regulators use to shape the epithelial cell epigenome to accommodate CFTR expression.

项目总结:

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

LINE-1 promotes tumorigenicity and exacerbates tumor progression via stimulating metabolism reprogramming in non-small cell lung cancer.

DOI：
10.1186/s12943-022-01618-5
发表时间：
2022-07-16
期刊：
MOLECULAR CANCER
影响因子：
37.3
作者：
Sun, Zeguo;Zhang, Rui;Zhang, Xiao;Sun, Yifei;Liu, Pengpeng;Francoeur, Nancy;Han, Lei;Lam, Wan Yee;Yi, Zhengzi;Sebra, Robert;Walsh, Martin;Yu, Jinpu;Zhang, Weijia
通讯作者：
Zhang, Weijia

Single cell full-length transcriptome of human subcutaneous adipose tissue reveals unique and heterogeneous cell populations.

DOI：
10.1016/j.isci.2022.104772
发表时间：
2022-08-19
期刊：
ISCIENCE
影响因子：
5.8
作者：
Whytock, Katie L;Sun, Yifei;Divoux, Adeline;Yu, GongXin;Smith, Steven R;Walsh, Martin J;Sparks, Lauren M
通讯作者：
Sparks, Lauren M