Determination of a Novel Epigenetic Silencing Mechanism

新型表观遗传沉默机制的确定

基本信息

批准号：
9099408
负责人：
Ke Zhang Reid
金额：
$ 42.03万
依托单位：
WAKE FOREST UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9099408
关键词：
5&apos -exoribonuclease Affinity Chromatography Aging Binding Proteins Biological Assay Biology Cell physiology Cells Cellular biology Centromere Chemistry Chromatin Co-Immunoprecipitations Complex DNA Sequence Alteration Data Defect Development Doctor of Philosophy Endoribonucleases Environment Enzymes Epigenetic Process Etiology Eukaryota Exoribonucleases Fission Yeast Gene Expression Gene Expression Regulation Gene Silencing Genetic Genetic Transcription Genome Genomic approach Goals Growth and Development function Health Heterochromatin Human Link Maintenance Malignant Neoplasms Mass Spectrum Analysis Mediating Mediator of activation protein Methods Modeling Molecular Biology Organism Orthologous Gene Pathway interactions Phenotype Play Process Proteins Quality Control RNA RNA Interference RNA Interference Pathway RNA Processing Research Research Training Ribonucleases Ribosomal RNA Role Saccharomyces cerevisiae Saccharomycetales Small RNA Students Study models Syndrome Temperature Testing Transcript United States National Institutes of Health Universities Untranslated RNA Work base career chromatin immunoprecipitation college crosslink design epigenetic regulation epigenome exosome forest genetic analysis genetic information human disease innovation mutant novel poly A specific exoribonuclease programs protein protein interaction public health relevance transcription termination transcriptome undergraduate research

项目摘要

DESCRIPTION (provided by applicant): The Epigenome regulates when, where and how an organism uses the genetic information stored in its genome. It is essential to many cellular processes, such as the regulation of gene expression, genome organization and cell-fate determination. It also governs growth, development, and ultimately human health. Heterochromatin represents silenced chromatic domains, which are assembled and maintained through epigenetic mechanisms. Extensive studies have focused on the assembly of heterochromatin at centromeres mediated by the RNA interference (RNAi) pathway. Recent studies, including ours, indicate that the exosome, an RNA quality control and surveillance complex, performs in a parallel pathway with RNAi to mediate epigenetic silencing. Although both RNAi and the exosome pathways are RNA-mediated and involved in processing long noncoding RNAs (ncRNAs) into small RNAs, exactly how the exosome pathway participates in heterochromatin assembly is not been demonstrated. Whether other RNAi-independent RNA processing pathways participate in epigenetic silencing is also unknown. We have recently identified a RNA-processing mechanism in epigenetic silencing that works independently of both RNAi and the exosome. The proposed research aims are designed to test the hypothesis that Dhp1, a conserved 5' to 3' exoribonuclease and ortholog of budding yeast Rat1 and metazoan Xrn2, plays a heretofore unknown role in epigenetic silencing, beyond its established role in transcription termination. Genetic, cell biology, and genomic approaches will be employed to investigate: 1) the localization of Dhp1 at heterochromatic regions; 2) Dhp1 binding proteins; and 3) the enzymatic activity of Dhp1 and potential co-activators in epigenetic silencing. Results will clarify how various RNA-processing pathways, acting together or independently, contribute to epigenetic regulation of the eukaryotic genome, a fundamental mechanism of gene expression. This study will be carried out in fission yeast, Schizosaccharomyces pombe (S. pombe), a premier model for studying epigenetic silencing because of its conserved epigenetic components and suitability for powerful combinatory experimental methods as well as undergraduate research. This project is significant and innovative. It will define a novel RNA-processing mechanism in epigenetic silencing that works independently of both RNAi and the exosome. Additionally, it will be the first exploration into how Dhp1/Rat1/Xrn2 functions in chromatin-based silencing.

描述（通过应用证明）：表观基因组在何时，何处和如何使用其基因组中的遗传学遗传学在表观遗传机制（RNAi）途径（包括我们的）中，人类的生长，发展和最终的健康状况。尽管RNAi和外部途径都是RNA介导的，并且涉及将长的不编码RNA（NCRNA）加入小RNA，而异染色质组装中的外染色体途径也是如此。拟议的研究目的是为了假设，dhp1 g的酵母菌和后生XRN2在表观遗传沉默中扮演未知的作用，超越了转录终止和基因组。 1）ATIC区域的位置；研究将在裂变酵母中进行，Schizosacchomyces Pombe（S. Pombe）是研究其共同组成部分的首要模型，适合性的组合性thods和本质上的研究。而且，外泌体。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Novel Epigenetic Silencing Pathway Involving the Highly Conserved 5'-3' Exoribonuclease Dhp1/Rat1/Xrn2 in Schizosaccharomyces pombe.

DOI：
10.1371/journal.pgen.1005873
发表时间：
2016-02
期刊：
PLoS genetics
影响因子：
4.5
作者：
Tucker JF;Ohle C;Schermann G;Bendrin K;Zhang W;Fischer T;Zhang K
通讯作者：
Zhang K

The fission yeast MTREC and EJC orthologs ensure the maturation of meiotic transcripts during meiosis.

DOI：
10.1261/rna.055608.115
发表时间：
2016-09
期刊：
RNA (New York, N.Y.)
影响因子：
0
作者：
Marayati BF;Hoskins V;Boger RW;Tucker JF;Fishman ES;Bray AS;Zhang K
通讯作者：
Zhang K

Loss of Elongation-Like Factor 1 Spontaneously Induces Diverse, RNase H-Related Suppressor Mutations in Schizosaccharomyces pombe.

DOI：
10.1534/genetics.118.301055
发表时间：
2018-08
期刊：
Genetics
影响因子：
3.3
作者：
Marayati BF;Drayton AL;Tucker JF;Huckabee RH;Anderson AM;Pease JB;Zeyl CW;Zhang K
通讯作者：
Zhang K

A Deep-sequencing-assisted, Spontaneous Suppressor Screen in the Fission Yeast Schizosaccharomyces pombe.

裂殖酵母裂殖酵母中的深度测序辅助自发抑制子筛选。