权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Characterization of a novel family of human transcription factors that bind at +240 downstream of the transcription start site.

结合在转录起始位点下游 240 处的新型人类转录因子家族的表征。

基本信息

批准号：
10361502
负责人：
PEGGY J Farnham
金额：
$ 33万
依托单位：
UNIVERSITY OF SOUTHERN CALIFORNIA
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：
2020-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10361502
关键词：
Affect Binding Binding Sites Biological Assay C2H2 Zinc Finger CRISPR/Cas technology Cell Line Cell Proliferation Cells ChIP-seq Chromatin Chromatin Structure CpG Islands DNA Binding DNA Binding Domain DNA Methylation Disease Elements Failure Family Family member Female Genes Genetic Transcription Human Human Cell Line Investigation Lead Location Maps Mediating Nuclear Extract Nucleosomes Pattern Positioning Attribute Promoter Regions Proteins Proteomics RNA Reporter Role Series Techniques Testing Transcription Elongation Transcription Initiation Transcription Initiation Site Transcriptional Regulation X Chromosome Y Chromosome ZFY protein Zinc Fingers cell type epigenomics genome-wide analysis histone modification human disease insight novel novel therapeutics promoter protein protein interaction protein structure recruit transcription factor transcriptome transcriptomics

项目摘要

Our study focuses on a family of human C2H2 zinc finger proteins composed of ZFX, ZFY, and ZNF711 which are expressed in all human cell types. In our preliminary studies, we show that deletion of ZFX family members has severe detrimental consequences on cell proliferation. We have performed ChIP- seq assays for ZFX, ZFY, and ZNF711 in several different human cell lines. Interestingly, we found that these TFs have identical binding patterns at the same CpG island promoter regions, with an average peak of binding at +240bp downstream of the transcription start site. Although their protein structure suggests that ZFX, ZFY, and ZNF711 are transcriptional regulators, the mechanisms by which they influence transcription have not yet been elucidated. Our preliminary results suggest that the ZXF family members are important regulators of the human transcriptome. A failure to properly regulate the transcriptome can lead to many types of human disease. Therefore, a thorough characterization of this family of TFs is of critical importance. Two of the family members (ZFX and ZFY) are essentially identical proteins encoded on either the X or Y chromosome, whereas ZNF711 has 67% overall similarity with ZFX and 87% similarity in the zinc finger domain. Because ZFX and ZFY are basically identical proteins, we will focus on a comparison of ZFX and ZNF711 using a female cell line (which lacks ZFY). We propose to characterize the mechanisms by which these factors regulate transcription using a 3-pronged approach. In Aim 1, we will perform detailed investigations of ZFX and ZNF711 binding to determine how these transcription factors are recruited to CpG island promoters. In Aim 2, we will identify critical regulatory domains and interacting proteins of ZFX and ZNF711. In Aim 3, we will characterize the mechanism by which ZFX and ZNF711 mediate transcriptional regulation. Importantly, each of the Aims can be performed independently of the others and can begin immediately. Through the combination of Aims 1-3, we will thoroughly characterize the function of the ZFX family using epigenomic, proteomic, and transcriptomic approaches. Completion of our proposed studies will provide new insights into transcriptional regulation and chromatin structure at human CpG island promoters.

我们的研究重点是一个由ZFX、ZFY和ZNF711组成的人C2H2锌指蛋白家族