Position effects on gene expression level and noise
Position effects on gene expression level and noise
批准号:
9342995
负责人:
JIANZHI ZHANG
金额:
$30.1万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-09-01 至 2020-05-31
关键词:
AniridiaBiological ModelsBiotechnologyBrainCellsCessation of lifeChromatinChromosomal RearrangementCodeDNA Replication TimingDataDiseaseEmbryoEnvironmentEpigenetic ProcessEssential GenesEuchromatinEukaryotaEvolutionFluorescence-Activated Cell SortingGalactoseGalectin 1Gene ClusterGene DuplicationGene ExpressionGene Expression RegulationGene ProteinsGene StructureGenesGeneticGenomeGenomic SegmentGenomicsHereditary DiseaseHeterochromatinHoloprosencephalyHumanIndividualInfertilityIrisKnowledgeLifeLightLinkLocationMeasuresMetabolic PathwayModelingMolecularMolecular GeneticsNoiseNucleosomesOrganPathway interactionsPatternPhenotypePositioning AttributeProteinsResearchRoleSaccharomyces cerevisiaeSaccharomycetalesSeriesTestingTimeTissuesTransgenesTransgenic OrganismsVariantYeastschromosomal locationdeafnessdevelopmental diseasedriving forceduplicate genesexperimental studyfitnessgenetic technologygenome-widehistone modificationhuman diseasemutantprogramspromoterprotein complexprotein expressionpublic health relevancescale upsexsuccesssynthetic biologytraittransgene expressionwhole genome
中文摘要
项目概要
我的研究计划的长期目标是了解分子遗传机制和
表型变异和进化的驱动力,其中表型可能是分子、细胞、组织、
器官、组织或其他层面。基因表达是分子水平上的表型特征,对于
所有形式的生命。该提案集中于基因表达的一个方面,即位置效应,即位置效应
基因的染色体位置对其活性的影响。位置效应与
许多遗传性疾病,如性逆转、无虹膜症(虹膜缺失)和前脑无裂畸形(大脑
通常会导致胚胎死亡的发育障碍)。任何由以下原因引起的遗传病
不破坏基因结构的染色体重排可以被视为位置的结果
效果。位置效应在转基因生物中已被多次观察到,揭示了位置效应的重要性
转基因在其表达时被置于基因组中的位置。位置效应也已被调用
解释基因组组织的多个非随机特征。尽管它很重要,但我们的
关于位置效应的模式和机制的知识是有限的,并且关于位置效应的许多假设
位置效应尚未测试。过去关于位置效应的研究主要集中在异染色质的作用上
忽略绝大多数基因所在的常染色质(并在突变体和突变体中易位)
进化)。位置对平均蛋白质表达和表达噪声影响的基因组研究
建议使用芽殖酵母酿酒酵母。生成的数据将用于探测一般情况
位置效应的模式,研究位置效应的潜在遗传和表观遗传机制,以及
测试位置效应在基因组组织非随机特征形成中的作用。此外,
将在酵母中进行一系列操作实验,以测试以前未被认识到的作用
功能相关基因染色体聚类起源中表达噪声的位置效应。
总体而言,该项目预计将(i)提供前所未有的全基因组位置效应信息
酵母中的基因表达和表达噪音,(ii) 揭示位置的分子和机制基础
效应,以及(iii)加深我们对位置效应在真核基因组进化中的作用的理解
组织。
英文摘要
Project Summary
The long-term objective of my research program is to understand the molecular genetic mechanisms and
driving forces of phenotypic variation and evolution, where the phenotype may be at molecular, cellular, tissue,
organ, organismal or other levels. Gene expression is a phenotypic trait at the molecular level that is critical to
all forms of life. This proposal centers on one aspect of gene expression known as position effect, which refers
to the influence of the chromosomal location of a gene on its activity. Position effect has been implicated in a
number of genetic diseases such as sex reversal, aniridia (absence of iris), and holoprosencephaly (a brain
developmental disorder that typically leads to embryonic death). Any genetic disease caused by a
chromosomal rearrangement that does not disrupt gene structure may be regarded as a result of position
effect. Position effect has been observed many times in transgenic organisms, revealing the significance of the
location at which the transgene is placed in a genome on its expression. Position effect has also been invoked
in the explanations of multiple nonrandom features of genome organization. Despite its importance, our
knowledge about the pattern and mechanism of position effect is limited and many hypotheses regarding
position effect remain untested. Past studies of position effect focused on the role of heterochromatin, largely
ignoring euchromatin where the vast majority of genes are located (and translocated in mutants and in
evolution). A genomic study of position effects on mean protein expression and expression noise in the
budding yeast Saccharomyces cerevisiae is proposed. The generated data will be used to probe the general
patterns of position effects, to study the underlying genetic and epigenetic mechanisms of position effects, and
to test the role of position effects in the formation of nonrandom features of genome organization. Furthermore,
a series of manipulative experiments will be conducted in yeast to test a previously unrecognized role of
position effect on expression noise in the origin of chromosomal clustering of functionally related genes.
Overall, this project is expected to (i) provide unprecedented genome-wide information of position effect on
gene expression and expression noise in yeast, (ii) uncover the molecular and mechanistic basis of position
effects, and (iii) deepen our understanding of the role of position effect in the evolution of eukaryotic genome
organization.
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